2022/01/25 更新

写真a

サエキ マキオ
佐伯 万騎男
SAEKI Makio
所属
教育研究院 医歯学系 歯学系列 教授
医歯学総合研究科 口腔生命科学専攻 顎顔面再建学 教授
職名
教授
外部リンク

学位

  • 博士(歯学) ( 2000年6月   大阪大学 )

研究キーワード

  • R2TP複合体

  • Monad

  • 腫瘍

  • Pharmacology

  • Neuropharmacology

研究分野

  • ライフサイエンス / 常態系口腔科学  / 歯科薬理学

経歴(researchmap)

  • 新潟大学 大学院医歯学総合研究科 歯科薬理学分野 教授

    2014年2月

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  • 大阪大学 大学院歯学研究科 統合機能口腔科学専攻   助手

    1995年4月

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経歴

  • 新潟大学   医歯学総合研究科 口腔生命科学専攻 顎顔面再建学   教授

    2014年2月 - 現在

学歴

  • 大阪大学

    - 1995年

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  • 大阪大学   歯学部

    - 1995年

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    国名: 日本国

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所属学協会

 

論文

  • Effects of rice fermented extracts, "Sake Lees", on the functional activity of odontoblast-like cells (KN-3 cells).

    Keiichiro Okamoto, Yoshito Kakihara, Naoto Ohkura, Aiko Tohma, Ayako Washio, Chiaki Kitamura, Yuichiro Noiri, Kensuke Yamamura, Makio Saeki

    Odontology   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study was designed to investigate the effects of Sake Lees extracts (SLE, Sake Kasu) on the functional activity of odontoblastic cells and tooth pulp of the rats. For in vitro studies, a rat clonal odontoblast-like cell line, KN-3 cells were cultured. SLE significantly decreased KN-3 cell proliferation, but showed no significant cytotoxicity. SLE effects on several protein productions of KN-3 cells were compared with PBS. SLE and PBS increased alkaline phosphatase (ALP), dentin sialoprotein (DSP), and osterix in a day-course dependent manner, while SLE increased the induction of ALP on day 9-21 and DSP on day 15-21. SLE also increased Runx2 expression on day 3 and 9 compared to PBS. Alizarin Red stainings revealed that SLE showed a subtle increase in mineralization of KN-3 cells on day 15 and 21. A histological investigation was conducted to assess if SLE induced reparative dentin formation after direct capping at the exposed tooth pulp in rats, suggesting that SLE could increase the reparative dentin formation more than PBS. These findings suggest that Sake Lees could have functional roles in the alterations of odontoblastic activity, which might influence the physiology of the tooth pulp.

    DOI: 10.1007/s10266-021-00654-9

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  • HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma

    Akihiko Nakamura, Yoshito Kakihara, Akinori Funayama, Kenta Haga, Toshihiko Mikami, Daiki Kobayashi, Yutaka Yoshida, Kenji Izumi, Tadaharu Kobayashi, Makio Saeki

    Biochemical and Biophysical Research Communications   557   294 - 301   2021年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bbrc.2021.04.021

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  • Identification and characterization of R2TP in the development of oral squamous cell carcinoma

    Tetsuo Kiguchi, Yoshito Kakihara, Manabu Yamazaki, Kouji Katsura, Kenji Izumi, Jun-ichi Tanuma, Takashi Saku, Ritsuo Takagi, Makio Saeki

    Biochemical and Biophysical Research Communications   548   161 - 166   2021年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bbrc.2021.02.074

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  • R2TP/PAQosome as a promising chemotherapeutic target in cancer. 査読 国際誌

    Yoshito Kakihara, Tetsuo Kiguchi, Atsushi Ohazama, Makio Saeki

    The Japanese dental science review   56 ( 1 )   38 - 42   2020年12月

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    記述言語:英語  

    R2TP/PAQosome (particle for arrangement of quaternary structure) is a novel multisubunit chaperone specialized in the assembly/maturation of protein complexes that are involved in essential cellular processes such as PIKKs (phosphatidylinositol 3-kinase-like kinases) signaling, snoRNP (small nucleolar ribonucleoprotein) biogenesis, and RNAP II (RNA polymerase II) complex formation. In this review article, we describe the current understanding of R2TP/PAQosome functions and characteristics as well as how the chaperone complex is involved in oncogenesis, highlighting DNA damage response, mTOR (mammalian target of rapamycin) pathway as well as snoRNP biogenesis. Also, we discuss its possible involvement in HNSCC (head and neck squamous cell carcinoma) including OSCC (oral squamous cell carcinoma). Finally, we provide an overview of current anti-cancer drug development efforts targeting R2TP/PAQosome.

    DOI: 10.1016/j.jdsr.2019.08.001

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  • Reptinは胎仔上皮におけるDNA損傷応答を介して器官形成を制御する

    目黒 史也, 柿原 嘉人, 川崎 真依子, 川崎 勝盛, 丹原 惇, トゥラカナン・スッパラック, 工藤 武久, 山田 茜, 前田 健康, 多部田 康一, 佐伯 万騎男, 大峡 淳

    新潟歯学会雑誌   50 ( 2 )   115 - 116   2020年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • IFT20 is critical for collagen biosynthesis in craniofacial bone formation. 国際誌

    Hiroyuki Yamaguchi, Masahiko Terajima, Megumi Kitami, Jianbo Wang, Li He, Makio Saeki, Mitsuo Yamauchi, Yoshihiro Komatsu

    Biochemical and biophysical research communications   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intraflagellar transport (IFT) is essential for assembling primary cilia required for bone formation. Disruption of IFT frequently leads to bone defects in humans. While it has been well studied about the function of IFT in osteogenic cell proliferation and differentiation, little is known about its role in collagen biosynthesis during bone formation. Here we show that IFT20, the smallest IFT protein in the IFT-B complex, is important for collagen biosynthesis in mice. Deletion of Ift20 in craniofacial osteoblasts displayed bone defects in the face. While collagen protein levels are unaffected by loss of Ift20, collagen cross-linking was significantly altered. In both Ift20:Wnt1-Cre and Ift20:Ocn-Cre mice the bones exhibit increased hydroxylysine-aldehyde deived cross-linking, and decreased lysine-aldehyde derived cross-linking. To obtain insight into the molecular mechanisms, we examined the expression levels of telopeptidyl lysyl hydroxylase 2 (LH2), and associated chaperone complexes. The results demonstrated that, while LH2 levels were unaffected by loss of Ift20, its chaperone, FKBP65, was significantly increased in Ift20:Wnt1-Cre and Ift20:Ocn-Cre mouse calvaria as well as femurs. These results suggest that IFT20 plays a pivotal role in collagen biosynthesis by regulating, in part, telopeptidyl lysine hydroxylation and cross-linking in bone. To the best of our knowledge, this is the first to demonstrate that the IFT components control collagen post-translational modifications. This provides a novel insight into the craniofacial bone defects associated with craniofacial skeletal ciliopathies.

    DOI: 10.1016/j.bbrc.2020.09.033

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  • リボソーム合成関連因子HEATR1は、Pontin/Reptin complexと共に口腔扁平上皮癌進展に寄与する

    中村 彬彦, 木口 哲郎, 高木 律男, 船山 昭典, 小林 正治, 柿原 嘉人, 佐伯 万騎男

    日本口腔科学会雑誌   69 ( 2 )   132 - 132   2020年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本口腔科学会  

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  • ROCK inhibitors enhance bone healing by promoting osteoclastic and osteoblastic differentiation. 査読 国際誌

    Juri Nakata, Yosuke Akiba, Jun Nihara, Lay Thant, Kaori Eguchi, Hiroko Kato, Kenji Izumi, Mariko Ohkura, Masanori Otake, Yoshito Kakihara, Isao Saito, Makio Saeki

    Biochemical and biophysical research communications   2020年3月

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    記述言語:英語  

    Osteoclast and osteoblast are essential for proper bone development and remodeling as well as recovery of bone fracture. In this study, we seek chemical compounds that enhance turnover of bone metabolism for promoting bone healing. First, we screen a chemical library which includes 378 compounds by using murine pre-osteoclastic RAW264.7 cells to identify compounds that promote osteoclastic differentiation. We find that two ROCK (Rho-associated coiled-coil kinase) inhibitors, HA-1077 (Fasudil) and Y-27632, enhance osteoclastogenesis. Subsequently, we identify that these two compounds also increase osteoblastic differentiation of MC3T3-E1 cells. Finally, our in vivo experiment shows that the local administration of ROCK inhibitors accelerate the bone healing of the rat calvarial defect.

    DOI: 10.1016/j.bbrc.2020.03.033

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  • Gli3 is a Key Factor in the Schwann Cells from Both Intact and Injured Peripheral Nerves. 査読 国際誌

    Yurie Yamada, Supaluk Trakanant, Jun Nihara, Takehisa Kudo, Kenji Seo, Makio Saeki, Masayuki Kurose, Daisuke Matsumaru, Takeyasu Maeda, Atsushi Ohazama

    Neuroscience   432   229 - 239   2020年2月

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    記述言語:英語  

    Hedgehog (Hh) signaling has been shown to be involved in regulating both intact and injured peripheral nerves. Therefore, it is critical to understand how Hh signaling is regulated in the peripheral nerve. One of the transcription factors of the Hh signaling pathway, Gli3, functions as both a repressor and an activator of Hh signaling activity. However, it remains unclear whether Gli3 is involved in controlling the intact and/or injured peripheral nerves. We found that Gli3 act as a repressor in the Schwann cells (SCs) of intact sciatic nerves. Although Dhh and Ptch1 expression were present, Hh signaling was not activated in these SCs. Moreover, heterozygous Gli3 mutation (Gli3-/+) induced ectopic Hh signaling activity in SCs. Hh signaling was thus suppressed by Gli3 in the SCs of intact sciatic nerves. Minor morphological changes were observed in the intact nerves from Gli3-/+ mice. Gli3 expression was significantly decreased following injury and ligand expression switched from Dhh to Shh, which activated Hh signaling in SCs from wild-type mice. Changes of these ligands was found to be important for nerve regeneration in which the downregulation of Gli3 was also involved. In fact, Gli3-/+ mice exhibited accelerated ligand switching and subsequent nerve regeneration. Both suppression of Hh signaling with Gli3 in the intact nerves and activation of Hh signaling without Gli3 in the injured nerve were observed in the SCs in an autocrine manner. Thus, Gli3 is a key factor in the control of intact peripheral nerve homeostasis and nerve regeneration.

    DOI: 10.1016/j.neuroscience.2020.02.036

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  • Daily administration of Sake Lees (Sake Kasu) reduced psychophysical stress-induced hyperalgesia and Fos responses in the lumbar spinal dorsal horn evoked by noxious stimulation to the hindpaw in the rats. 査読

    Shimizu S, Nakatani Y, Kakihara Y, Taiyoji M, Saeki M, Takagi R, Yamamura K, Okamoto K

    Bioscience, Biotechnology, and Biochemistry   84 ( 1 )   159 - 170   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/09168451.2019.1662278

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  • Bmp signaling in molar cusp formation. 査読 国際誌

    Fumiya Meguro, Thantrira Porntaveetus, Maiko Kawasaki, Katsushige Kawasaki, Akane Yamada, Yoshito Kakihara, Makio Saeki, Koichi Tabeta, John A Kessler, Takeyasu Maeda, Atsushi Ohazama

    Gene expression patterns : GEP   32   67 - 71   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tooth cusp is a crucial structure, since the shape of the molar tooth is determined by number, shape, and size of the cusp. Bone morphogenetic protein (Bmp) signaling is known to play a critical role in tooth development, including in initiation. However, it remains unclear whether Bmp signaling is also involved in cusp formation. To address this question, we examined cusp in two different transgenic mouse lines: mice with overexpression of Bmp4 (K14-Bmp4), and those with Bmp inhibitor, Noggin, (K14-Noggin) under keratin14 (K14) promoter. K14-Noggin mice demonstrated extra cusps, whereas reduced number of cusps was observed in K14-Bmp4 mice. To further understand how Bmps are expressed during cusp formation, we performed whole-mount in situ hybridisation analysis of three major Bmps (Bmp2, Bmp4, and Bmp7) in murine maxillary and mandibular molars from E14.5 to P3. The linear expressions of Bmp2 and Bmp4 were observed in both maxillary and mandibular molars at E14.5. The expression patterns of Bmp2 and Bmp4 became significantly different between the maxillary and mandibular molars at E16.5. At P3, all Bmps were expressed in all the cusp regions of the maxillary molar; however, the patterns differed. All Bmps thus exhibited dynamic temporo-spatial expression during the cusp formation. It could therefore be inferred that Bmp signaling is involved in regulating cusp formation.

    DOI: 10.1016/j.gep.2019.04.002

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  • Japanese Rice Wine can reduce psychophysical stress-induced depression-like behaviors and Fos expression in the trigeminal subnucleus caudalis evoked by masseter muscle injury in the rats. 査読

    Nakatani Y, Kakihara Y, Shimizu S, Kurose M, Sato T, Kaneoke M, Saeki M, Takagi R, Yamamura K, Okamoto K

    Bioscience, biotechnology, and biochemistry   1 - 11   2018年10月

  • Binding of PICK1 PDZ domain with calcineurin B regulates osteoclast differentiation 査読

    Yuya Kamano, Jun Watanabe, Tsutomu Iida, Takeru Kondo, Hiroko Okawa, Hirofumi Yatani, Makio Saeki, Hiroshi Egusa

    Biochemical and Biophysical Research Communications   496 ( 1 )   83 - 88   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier B.V.  

    The calcineurin/nuclear factor of activated T cell (NFAT) signaling pathway plays a major role in osteoclast differentiation
    however, the proteins that react with the calcineurin-NFAT complex in osteoclasts to regulate osteoclastogenesis remain unclear. Here, we present evidence that PICK1 also positively regulates calcineurin B in osteoclasts to activate NFAT to promote osteoclastogenesis. mRNA and protein expression of PICK1 in murine primary bone marrow macrophages (BMMs) was significantly increased during RANKL-induced osteoclast differentiation. The interaction of PICK1 with calcineurin B in BMMs was confirmed by co-immunoprecipitation. An inhibitor of the PICK1 PDZ domain significantly decreased osteoclastogenesis marker gene expression and the number of TRAP-positive multinucleated cells among RAW264.7 osteoclast progenitor cells. Overexpression of PICK1 in RAW264.7 cells significantly increased the number of TRAP-positive mature osteoclasts. Increased NFAT activation with transcriptional activation of PICK1 during RAW264.7 osteoclastogenesis was also confirmed in a tetracycline-controlled PICK1 expression system. These results suggest that the PDZ domain of PICK1 directly interacts with calcineurin B in osteoclast progenitor cells and promotes osteoclast differentiation through activation of calcineurin-NFAT signaling.

    DOI: 10.1016/j.bbrc.2017.12.173

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  • The effect of ROCK inhibitor on bone remodeling 査読

    Juri Nakata, Yosuke Akiba, Kaori Eguchi, Jun Nihara, Isao Saito, Yoshito Kakihara, Makio Saeki

    JOURNAL OF BONE AND MINERAL RESEARCH   32   S229 - S229   2017年12月

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    記述言語:英語   出版者・発行元:WILEY  

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  • Gene delivery and expression systems in induced pluripotent stem cells 招待

    Zhang M, Niibe K, Kondo T, Kamano Y, Saeki M, Egusa H

    Interface Oral Health Science 2016, Springer   121 - 133   2017年

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    記述言語:英語  

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  • GSK-3 beta inhibitory activities of novel dichroloresorcinol derivatives from Cosmospora vilior isolated from a mangrove plant 査読

    Shiono Yoshihito, Miyazaki Nozomi, Murayama Tetsuya, Koseki Takuya, Harizon, Katja Dewa Gede, Supratman Unang, Nakata Juri, Kakihara Yoshito, Saeki Makio, Yoshida Jun, Uesugi Shota, Kimura Ken-ichi

    PHYTOCHEMISTRY LETTERS   18   122 - 127   2016年12月

  • The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis. 査読

    Akiba Y, Mizuta A, Kakihara Y, Nakata J, Nihara J, Saito I, Egusa H, Saeki M

    Biochemistry and biophysics reports   5   253 - 258   2016年3月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbrep.2015.12.011

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  • Discovering novel drugs for modulating osteoclastogenesis 査読

    Kakihara Yoshito, Nakata Juni, Kiyokawa Yuki, Yamashita Naoyuki, Shiono Yoshihito, Saeki Makio

    JOURNAL OF PHARMACOLOGICAL SCIENCES   130 ( 3 )   S208   2016年3月

  • Gingival fibroblasts as autologous feeders for induced pluripotent stem cells 査読

    Yu G, Okawa H, Okita K, Kamano Y, Wang F, Saeki M, Yatani H, Egusa H

    J Dent Res   95 ( 1 )   110 - 118   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/0022034515611602

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  • Controlled Osteogenic Differentiation of Mouse Mesenchymal Stem Cells by Tetracycline-Controlled Transcriptional Activation of Amelogenin 査読

    Fangfang Wang, Hiroko Okawa, Yuya Kamano, Kunimichi Niibe, Hiroki Kayashima, Thanaphum Osathanon, Prasit Pavasant, Makio Saeki, Hirofumi Yatani, Hiroshi Egusa

    PLOS ONE   10 ( 12 )   e0145677   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Regenerative dental therapies for bone tissues rely on efficient targeting of endogenous and transplanted mesenchymal stem cells (MSCs) to guide bone formation. Amelogenin is the primary component of Emdogain, which is used to regenerate periodontal defects; however, the mechanisms underlying the therapeutic effects on alveolar bone remain unclear. The tetracycline (Tet)-dependent transcriptional regulatory system is a good candidate to investigate distinct roles of genes of interest during stem cell differentiation. Here, we investigated amelogenin-dependent regulation of osteogenesis in MSCs by establishing a Tet-controlled transcriptional activation system. Clonal mouse bone marrow-derived MSCs were lentivirally transduced with the Tet repressor (TetR) expression vector followed by drug selection to obtain MSCs constitutively expressing TetR (MSCs-TetR). Expression vectors that contained the Tet operator and amelogenin-coding (Amelx) cDNA fragments were constructed using the Gateway system and lentivirally introduced into MSCs-TetR to generate a Tet regulation system in MSCs (MSCs-TetR/Amelx). MSCs-TetR/Amelx significantly overexpressed the Amelx gene and protein in the presence of the tetracycline derivative doxycycline. Concomitant expression of osterix, bone sialoprotein (BSP), osteopontin, and osteocalcin was modulated by addition or removal of doxycycline under osteogenic guidance. During osteogenic induction, MSCs-TetR/Amelx treated with doxycycline showed significantly increased gene expression of osterix, type I collagen, BSP, and osteocalcin in addition to increased alkaline phosphatase activity and mineralized nodule formation. Enhanced extracellular matrix calcification was observed when forced Amelx expression commenced at the early stage but not at the intermediate or late stages of osteogenesis. These results suggest that a Tet-controlled Amelx gene regulation system for mouse MSCs was successfully established, in which transcriptional activation of Amelx was associated with enhanced osteogenic differentiation, especially in the early stage of biomineralization.

    DOI: 10.1371/journal.pone.0145677

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  • The effect of CDK inhibitors on osteoclast differentiation 査読

    Kakihara Yoshito, Nakata Juri, Akiba Yosuke, Egusa Hiroshi, Saeki Makio

    JOURNAL OF PHARMACOLOGICAL SCIENCES   128 ( 3 )   S242   2015年7月

  • The R2TP chaperone complex: Its involvement in snoRNP assembly and tumorigenesis 査読

    Yoshito Kakihara, Makio Saeki

    Biomolecular Concepts   5 ( 6 )   513 - 520   2014年12月

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    記述言語:英語   出版者・発行元:De Gruyter Mouton  

    R2TP was originally identified in yeast Saccharomyces cerevisiae as Hsp90 interacting complex, and is composed of four different proteins: Rvb1, Rvb2, Tah1, and Pih1. This complex is well-conserved in eukaryotes, and is involved in many cellular processes such as snoRNP biogenesis, RNA polymerase assembly, PIKK signaling, and apoptosis. An increasing number of research related to R2TP suggests a linkage of its function with tumorigenesis. In this review, we provide an overview of several recent studies on R2TP that are related to cell proliferation and carcinogenesis, and propose a possible role of R2TP in tumorigenesis through regulating snoRNA/snoRNP biogenesis.

    DOI: 10.1515/bmc-2014-0028

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  • [Novel strategies for the development of anabolic agents for treatment of osteoporosis]. 査読

    Saeki M, Egusa H

    Nihon yakurigaku zasshi. Folia pharmacologica Japonica   144 ( 6 )   277 - 280   2014年12月

  • Comparative Analysis of Mouse-Induced Pluripotent Stem Cells and Mesenchymal Stem Cells During Osteogenic Differentiation In Vitro 査読

    Hiroshi Egusa, Hiroki Kayashima, Jiro Miura, Shinya Uraguchi, Fangfang Wang, Hiroko Okawa, Jun-Ichi Sasaki, Makio Saeki, Takuya Matsumoto, Hirofumi Yatani

    STEM CELLS AND DEVELOPMENT   23 ( 18 )   2156 - 2169   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT, INC  

    Induced pluripotent stem cells (iPSCs) can differentiate into mineralizing cells and are, therefore, expected to be useful for bone regenerative medicine; however, the characteristics of iPSC-derived osteogenic cells remain unclear. Here, we provide a direct in vitro comparison of the osteogenic differentiation process in mesenchymal stem cells (MSCs) and iPSCs from adult C57BL/6J mice. After 30 days of culture in osteogenic medium, both MSCs and iPSCs produced robustly mineralized bone nodules that contained abundant calcium phosphate with hydroxyapatite crystal formation. Mineral deposition was significantly higher in iPSC cultures than in MSC cultures. Scanning electron microscopy revealed budding matrix vesicles in early osteogenic iPSCs; subsequently, the vesicles propagated to exhibit robust mineralization without rich fibrous structures. Early osteogenic MSCs showed deposition of many matrix vesicles in abundant collagen fibrils that became solid mineralized structures. Both cell types demonstrated increased expression of osteogenic marker genes, such as runx2, osterix, dlx5, bone sialoprotein (BSP), and osteocalcin, during osteogenesis; however, real-time reverse transcription-polymerase chain reaction array analysis revealed that osteogenesis-related genes encoding mineralization-associated molecules, bone morphogenetic proteins, and extracellular matrix collagens were differentially expressed between iPSCs and MSCs. These data suggest that iPSCs are capable of differentiation into mature osteoblasts whose associated hydroxyapatite has a crystal structure similar to that of MSC-associated hydroxyapatite; however, the transcriptional differences between iPSCs and MSCs could result in differences in the mineral and matrix environments of the bone nodules. Determining the biological mechanisms underlying cell-specific differences in mineralization during in vitro iPSC osteogenesis may facilitate the development of clinically effective engineered bone.

    DOI: 10.1089/scd.2013.0344

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  • PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription 査読

    Yuya Kamano, Makio Saeki, Hiroshi Egusa, Yoshito Kakihara, Walid A. Houry, Hirofumi Yatani, Yoshinori Kamisaki

    FEBS Letters   587 ( 20 )   3303 - 3308   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PIH1D1 is the defining component of the R2TP complex. Recently, R2TP has been reported to stabilize mTOR (mammalian target of rapamycin), an important regulator of cell growth and protein synthesis. Two complexes of mTOR, mTORC1 and mTORC2, have been identified. We demonstrate that immunoprecipitation (IP) of PIH1D1 results in the co-IP of Raptor (mTORC1 specific), but not Rictor (mTORC2 specific), and that knockdown of PIH1D1 decreases mTORC1 assembly, S6 kinase phosphorylation (indicator of mTORC1 activity), and rRNA transcription without affecting mTORC2 in human breast cancer MCF-7 cells. In addition, we provide evidence that PIH1D1 is overexpressed in various breast cancer cell lines. These findings collectively suggest that PIH1D1 may have an important role in mTORC1 regulation in breast cancers. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2013.09.001

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  • Exosome-Bound WD Repeat Protein Monad Inhibits Breast Cancer Cell Invasion by Degrading Amphiregulin mRNA 査読

    Makio Saeki, Hiroshi Egusa, Yuya Kamano, Yoshito Kakihara, Walid A. Houry, Hirofumi Yatani, Shinzaburo Noguchi, Yoshinori Kamisaki

    PLOS ONE   8 ( 7 )   e67326   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Increased stabilization of mRNA coding for key cancer genes can contribute to invasiveness. This is achieved by down-regulation of exosome cofactors, which bind to 3'-UTR in cancer-related genes. Here, we identified amphiregulin, an EGFR ligand, as a target of WD repeat protein Monad, a component of R2TP/prefoldin-like complex, in MDA-MB-231 breast cancer cells. Monad specifically interacted with both the 3'-UTR of amphiregulin mRNA and the RNA degrading exosome, and enhanced decay of amphiregulin transcripts. Knockdown of Monad increased invasion and this effect was abolished with anti-amphiregulin neutralizing antibody. These results suggest that Monad could prevent amphiregulin-mediated invasion by degrading amphiregulin mRNA.

    DOI: 10.1371/journal.pone.0067326

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  • mTOR結合タンパク質PIH1D1がrRNA転写に及ぼす影響

    外園 真規, 佐伯 万騎男, 鎌野 優弥, 江草 宏, 上崎 善規

    日本薬理学雑誌   141 ( 3 )   30P - 30P   2013年3月

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  • RPAP3 splicing variant isoform 1 interacts with PIH1D1 to compose R2TP complex for cell survival 査読

    Miki Yoshida, Makio Saeki, Hiroshi Egusa, Yasuyuki Irie, Yuya Kamano, Shinya Uraguchi, Maki Sotozono, Hitoshi Niwa, Yoshinori Kamisaki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   430 ( 1 )   320 - 324   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We previously characterized RNA polymerase II-associated protein 3 (RPAP3) as a cell death enhancer. Here we report the identification and characterization of splicing isoform of RPAP3, isoform I and 2. We investigated the interaction between RPAP3 and PIH1 domain containing protein 1 (PIH1D1), and found that RPAP3 isoform 1, but not isoform 2, interacted with PIH1D1. Furthermore, knockdown of RPAP3 isoform 1 by small interfering RNA down-regulated PIH1D1 protein level without affecting PIH1D1 mRNA. RPAP3 isoform 2 potentiated doxorubicin-induced cell death in human breast cancer T-47 cells although isoform 1 showed no effect. These results suggest that R2TP complex is composed of RPAP3 isoform 1 for its stabilization, and that RPAP3 isoform 2 may have a dominant negative effect on the survival potency of R2TP complex. (C) 2012 Elsevier Inc. All rights reserved.

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  • Methamphetamine induces endoplasmic reticulum stress related gene CHOP/Gadd153/ddit3 in dopaminergic cells 査読

    Yasuyuki Irie, Makio Saeki, Hidekazu Tanaka, Yonehiro Kanemura, Shinpei Otake, Yoshiyuki Ozono, Toshisaburou Nagai, Yukiko Kondo, Kenzo Kudo, Yoshinori Kamisaki, Naomasa Miki, Eiichi Taira

    CELL AND TISSUE RESEARCH   345 ( 2 )   231 - 241   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    We examined the toxicity of methamphetamine and dopamine in CATH.a cells, which were derived from mouse dopamine-producing neural cells in the central nervous system. Use of the quantitative real-time polymerase chain reaction revealed that transcripts of the endoplasmic reticulum stress related gene (CHOP/Gadd153/ddit3) were considerably induced at 24-48 h after methamphetamine administration (but only under apoptotic conditions), whereas dopamine slightly induced CHOP/Gadd153/ddit3 transcripts at an early stage. We also found that dopamine and methamphetamine weakly induced transcripts for the glucose-regulated protein 78 gene (Grp78/Bip) at the early stage. Analysis by immunofluorescence microscopy demonstrated an increase ofaEuroEuroCHOP/Gadd153/ddit3 and Grp78/Bip proteins at 24 h after methamphetamine administration. Treatment of CATH.a cells with methamphetamine caused a re-distribution of dopamine inside the cells, which mimicked the presynaptic activity of neurons with cell bodies located in the ventral tegmental area or the substantia nigra. Thus, we have demonstrated the existence of endoplasmic reticulum stress in a model of presynaptic dopaminergic neurons for the first time. Together with the recent evidence suggesting the importance of presynaptic toxicity, our findings provide new insights into the mechanisms of dopamine toxicity, which might represent one of the most important mechanisms of methamphetamine toxicity and addiction.

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  • The small molecule harmine regulates NFATc1 and Id2 expression in osteoclast progenitor cells 査読

    Hiroshi Egusa, Masanori Doi, Makio Saeki, Sho Fukuyasu, Yoshihiro Akashi, Yoshifumi Yokota, Hirofumi Yatani, Yoshinori Kamisaki

    BONE   49 ( 2 )   264 - 274   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Small molecule compounds that potently affect osteoclastogenesis could be useful as chemical probes for elucidating the mechanisms of various biological phenomena and as effective therapeutic strategies against bone resorption. An osteoclast peogenitor cell-based high-throughput screening system was designed to target activation of NFAT, which is a key event for osteoclastogenesis. Orphan ligand library screening using this system identified the beta-carboline derivative harmine, which is a highly potent inhibitor of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A), to be an NFAT regulator in osteoclasts. RAW264.7 cells highly expressed DYRK1A protein, and in vitro phosphorylation assay demonstrated that harmine directly inhibited the DYRK1A-mediated phosphorylation (in-activation) of NFATc1. Harmine promoted the dephosphorylation (activation) of NFATc1 in RAW264.7 cells within 24 h, and it significantly increased the expression of NFATc1 in RAW264.7 cells and mouse primary bone marrow macrophages (BMMs) both in the presence and absence of RANKL stimulation. Although harmine promoted NFATc1 expression and stimulated target genes for osteoclastogenesis, cell-cell fusion and the formation of TRAP-positive multinucleated osteoclasts from RAW264.7 cells and BMMs was significantly inhibited by harmine treatment. Meanwhile, harmine remarkably promoted the expression of inhibitor of DNA binding/differentiation-2 (Id2), which is a negative regulator for osteoclastogenesis, in RAW264.7 cells and BMMs. An Id2-null-mutant showed slightly increased osteoclast formation from BMMs, and the harmine-mediated inhibition of osteoclast formation was abolished in the BMMs of Id2-null-mutant mice. These results suggest that harmine is a potent activator of NFATc1 that interferes with the function of DYRK1A in osteoclast precursors and also up-regulates Id2 protein, which may dominantly inhibit expression pathways associated with cell-cell fusion, thereby leading to the disruption of the fusion events mediating osteoclastogenesis. The small molecule harmine is therefore expected to provide an experimental tool for investigating signaling cascades in osteoclastogenesis, especially those centered on DYRK1A-mediated NFATc1 and Id2 regulation. (C) 2011 Elsevier Inc. All rights reserved.

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  • Monadはヒト乳がん細胞MDA-MB-231細胞の浸潤能を負に制御する

    成清 綾, 吉田 好紀, 佐伯 万騎男, 井上 美香, 島田 華奈, 江草 宏, 丹羽 均, 由良 義明, 矢谷 博文, 上崎 善規

    日本薬理学雑誌   137 ( 3 )   30P - 30P   2011年3月

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    記述言語:日本語   出版者・発行元:(公社)日本薬理学会  

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  • RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway 査読

    Kana Shimada, Makio Saeki, Hiroshi Egusa, Sho Fukuyasu, Yoshiaki Yura, Kazuhiro Iwai, Yoshinori Kamisaki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   404 ( 4 )   910 - 914   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Activation of anti-apoptotic gene transcription by NF-kappa B (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-kappa B essential modulator) interacts with a number of proteins and modulates the activity of NF-kappa B pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-kappa B pathway. These results indicate that RPAP3 may be a novel modulator of NF-kappa B pathway in apoptosis induced by anti-cancer chemotherapeutic agents. (C) 2010 Elsevier Inc. All rights reserved.

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  • PIH1D1, a subunit of R2TP complex, inhibits doxorubicin-induced apoptosis 査読

    Mika Inoue, Makio Saeki, Hiroshi Egusa, Hitoshi Niwa, Yoshinori Kamisaki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   403 ( 3-4 )   340 - 344   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We have previously reported that the two components of R2TP complex, RNA polymerase II-associated protein 3 (RPAP3), and Reptin, regulate apoptosis. Here we characterize another component of the complex, PIH1 domain containing protein 1 (PIH1D1). PIH1D1 interacts with both RPAP3 and Monad in HEK293 or U2OS cells. PIH1D1 transcripts were abundant in lung, leukocyte, and placenta. The reduction in endogenous PIH1D1 by siRNA enhanced apoptosis and caspase-3 activation induced by doxorubicin in U2OS cells. These results suggest that PIH1D1 may also function as a novel modulator of apoptosis pathway. (C) 2010 Elsevier Inc. All rights reserved.

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  • Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells 査読

    Hiroshi Egusa, Keisuke Okita, Hiroki Kayashima, Guannan Yu, Sho Fukuyasu, Makio Saeki, Takuya Matsumoto, Shinya Yamanaka, Hirofumi Yatani

    PLOS ONE   5 ( 9 )   e12743   2010年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Induced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort.
    Methodology/Principal Findings: We herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity.
    Conclusions/Significance: These results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection.

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  • A small-molecule approach to bone regenerative medicine in dentistry 査読

    Egusa H, Saeki M, Doi M, Fukuyasu S, Matsumoto T, Kamisaki Y, Yatani H

    Journal of Oral Biosciences   52 ( 2 )   107 - 118   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2330/joralbiosci.52.107

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  • Enhanced bone regeneration via multimodal actions of synthetic peptide SVVYGLR on osteoprogenitors and osteoclasts 査読

    Hiroshi Egusa, Yoshitoshi Kaneda, Yoshihiro Akashi, Yoshinosuke Hamada, Takuya Matsumoto, Makio Saeki, Devang K. Thakor, Yasuhiko Tabata, Nariaki Matsuura, Hirofumi Yatani

    BIOMATERIALS   30 ( 27 )   4676 - 4686   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Recently, the binding sequence Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR) was found adjacent to the RGD sequence in osteopontin, suggesting involvement in osteo-immune cross-talk. The aim of this study was to investigate bioactive functions of a synthetic SVVYGLR peptide in osteoprogenitor cells and osteoclasts, and to examine potential applications in bone regeneration. The SVVYGLR peptide significantly enhanced the adhesion and proliferation of several human mesenchymal cells including bone marrow-derived mesenchymal stem cells, and alpha v beta 3 integrin was involved in cell attachment to the peptide. Additionally, the peptide reduced the number of TRAP-positive multinucleated cells during osteoclastogenesis of RAW264.7 cells and normal murine pre-osteoclasts, and also suppressed NFAT activity and expression of osteoclastogenesis-related mRNAs. When standardized bone defects in rat calvariae were filled with a collagen sponge containing the peptide or PBS (control), the number of TRAP-positive osteoclasts in the grafted sites after 3 weeks was significantly lower in the peptide group. By the 5th week, significantly enhanced resorption of the grafted collagen sponge and new bone formation was observed within and surrounding the sponge in the peptide group. These data suggest that SVVYGLR is an effective bioactive peptide for bone tissue regeneration that promotes attachment and proliferation of osteogenic cells while also suppressing osteoclastogenesis. (C) 2009 Elsevier Ltd. All rights reserved.

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  • RPAP3 Interacts With Reptin to Regulate UV-Induced Phosphorylation of H2AX and DNA Damage 査読

    Lin Ni, Makio Saeki, Li Xu, Hirokazu Nakahara, Masafumi Saijo, Kiyoji Tanaka, Yoshinori Kamisaki

    JOURNAL OF CELLULAR BIOCHEMISTRY   106 ( 5 )   920 - 928   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    We have previously reported that Monad, a novel WD40 repeat protein, potentiates apoptosis induced by tumor necrosis factor-a and cycloheximide. By affinity purification and mass spectrometry, RNA polymerase II-associated protein 3 (RPAP3) was identified as a Monad binding protein and may function with Monad as a novel modulator of apoptosis pathways. Here we report that Reptin, a highly conserved AAA + ATPase that is part of various chromatin-remodeling complexes, is also involved in the association of RPAP3 by immunoprecipitation and confocal microscopic analysis. Overexpression of RPAP3 induced HEK293 cells to death after UV-irradiation. Loss of RPAP3 by RNAi improved HeLa cell survival after UV-induced DNA damage and attenuated the phosphorylation of H2AX. Depletion of Reptin reduced cell survival and facilitated the phosphorylation on H2AX. These results suggest that RPAP3 modulates UV-induced DNA damage by regulating H2AX phosphorylation. J. Cell. Biochem. 106: 920-928, 2009. (C) 2009 Wiley-Liss, Inc.

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  • PICK1 binds to calcineurin B and modulates the NFAT activity in PC12 cells 査読

    Tsutomu Iida, Hiroshi Egusa, Makio Saeki, Hirofumi Yatani, Yoshinori Kamisaki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   375 ( 4 )   655 - 659   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    In the central nervous system, calcineurin has been implicated in a number of Ca2+-sensitive pathways, including the regulation of neurotransmitter release and modulation of synaptic plasticity. PDZ domain-containing proteins also play an important role in the targeting and clustering of synaptic proteins. Using a yeast two-hybrid screen, we herein identified the PDZ domain-containing protein PICK1 as a specific interactor of calcineurin B. The interaction of calcineurin B and PICK1 was confirmed by GST pull-down assay in HEK293 cells and immunoprecipitation using rat brain lysate. Calcineurin B contains the consensus C-terminal peptide sequence required for interacting with the PDZ domain. The deletion of this sequence was sufficient to abolish the interaction between calcineurin B and PICK1. In addition, the knockdown of PICK1 by RNA interference inhibited the calcineurin-dependent activation of NFAT in PC12 cells. These results suggest that PICK1 may be a positive regulator of calcineurin in the central nervous system. (c) 2008 Elsevier Inc. All rights reserved.

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  • Molecular cloning of novel Monad binding protein containing tetratricopeptide repeat domains 査読

    Yuki Itsuki, Makio Saeki, Hirokazu Nakahara, Hiroshi Egusa, Yasuyuki Irie, Yutaka Terao, Shigetada Kawabata, Hirofumi Yatani, Yoshinori Kamisaki

    FEBS Letters   582 ( 16 )   2365 - 2370   2008年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have previously reported that Monad, a novel WD40 repeat protein, potentiates apoptosis induced by tumor necrosis factor-α(TNF-α) and cycloheximide (CHX). By affinity purification and mass spectrometry, we identified RNA polymerase II-associated protein 3 (RPAP3) as a binding protein of Monad. Overexpression of RPAP3 in HEK 293 potentiated caspase-3 activation and apoptosis induced by TNF-α and CHX. In addition, knockdown of RPAP3 by RNA interference resulted in a significant reduction of apoptosis induced by TNF-α and CHX in HEK293 and HeLa cells. These results raise the possibility that RPAP3, together with Monad, may function as a novel modulator of apoptosis pathway. Structured summary: MINT-6551090:Monad (uniprotkb:Q96MX6) physically interacts (MI:0218) with RPAP3 (uniprotkb:Q9H6T3) by anti tag coimmunoprecipitation (MI:0007)MINT-6551101, MINT-6551118:Monad (uniprotkb:Q96MX6) physically interacts (MI:0218) with RPAP3 (uniprotkb:Q9H6T3) by pull down (MI:0096)MINT-6551132:RPAP3 (uniprotkb:Q9H6T3) physically interacts (MI:0218) with Monad (uniprotkb:Q96MX6) by anti bait coimmunoprecipitation (MI:0006). © 2008 Federation of European Biochemical Societies.

    DOI: 10.1016/j.febslet.2008.05.041

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  • Calcineurin potentiates the activation of procaspase-3 by accelerating its proteolytic maturation 査読

    Makio Saeki, Yasuyuki Irie, Lin Ni, Yuki Itsuki, Yutaka Terao, Shigetada Kawabata, Yoshinori Kamisaki

    JOURNAL OF BIOLOGICAL CHEMISTRY   282 ( 16 )   11786 - 11794   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    We have previously shown that procaspase-3 exists in a high molecular weight complex in neonatal rat brain. Here, we purify and identify the protein that interacts with procaspase-3 from rat neonatal cortex. We searched binding proteins to procaspase-3 from a cytosolic extract of neonatal rat brain using chromatogram, two-dimensional gel electrophoresis, and far Western immunoblot. Analysis by tandem mass spectrometry identified the protein as a regulatory subunit of calcineurin ( calcineurin B). Overexpression of calcineurin B in HEK293 cells potentiated processing of caspase-3 and apoptosis triggered by tumor necrosis factor-alpha and cycloheximide treatment. In a cell-free system, overexpression of calcineurin B in HEK293 cells markedly increased processing of caspase-3 by cytochrome c. Immunodepletion of calcineurin B from cytosolic extracts from Jurkat cells decreased processing of caspase-3 by cytochrome c. Knockdown of calcineurin B by RNA interference resulted in reduced apoptosis in HEK293 cells but not in caspase-3-deficient MCF-7 cells. These results suggest that calcineurin B potentiates the activation of procaspase-3 by accelerating its proteolytic maturation.

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  • Monad, a WD40 repeat protein, promotes apoptosis induced by TNF-alpha 査読

    M Saeki, Y Irie, L Ni, M Yoshida, Y Itsuki, Y Kamisaki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   342 ( 2 )   568 - 572   2006年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    WD40 repeat proteins have a wide range of diverse biological functions including signal transduction, cell cycle regulation, RNA splicing, and transcription. Here we report the identification and characterization of a novel human WD40 repeat protein, Monad. Monad is unique, since it contains only two WD40 repeats. Monad is widely expressed in human tissues with the highest expression in testis. Overexpression of Monad in HEK293 cells potentiated apoptosis and caspase-3 activation induced by tumor necrosis factor-alpha and cycloheximide. These results raise the possibility that Monad may function as a novel modulator of apoptosis pathway. (c) 2006 Elsevier Inc. All rights reserved.

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  • Search for calcineurin B binding proteins by yeast two-hybrid system. 査読

    Yoshida M, Saeki M, Itsuki Y, Irie Y, Terao Y, Kawabata S, Hamada S, Niwa H, Kamisaki Y

    Journal of Pharmaceutical Sciences   97   217 - 217   2005年

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  • Formation of high molecular weight caspase-3 complex in neonatal rat brain 査読

    K Kurosu, M Saeki, Y Kamisaki

    NEUROCHEMISTRY INTERNATIONAL   44 ( 4 )   199 - 204   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Caspase-3 plays an essential role in normal brain development. Recently, a large protein complex known as apoptosome, which catalyzes the activation of caspase-3, has been reported. To investigate structural characteristics of caspase-3 in the developing brain, rat neonatal cortex extract was analysed by gel filtration chromatography. We show here the formation of high molecular complex including procaspase-3 in the extract. When the extract was activated by cytochrome c, caspase-3 recruitment to the apoptosome was not observed, although apoptotic protease activating factor-1 (Apaf-1), caspase-9, and X-linked inhibitor of apoptosis protein (XIAP) existed in the apoptosome. These results indicate that procaspase-3 exists as a high molecular weight complex during brain development. (C) 2003 Elsevier Ltd. All rights reserved.

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  • Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins 査読

    Y Irie, M Saeki, Y Kamisaki, E Martin, F Murad

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   100 ( 10 )   5634 - 5639   2003年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL ACAD SCIENCES  

    Several reports have described an activity that modifies nitrotyrosine-containing proteins and their immunoreactivity to nitrotyrosine Abs. Without knowing the product of the reaction, this new activity has been called a "denitrase." In those studies, some nonspecific proteins, which have multiple tyrosine residues, e.g., albumin, were used as a substrate. Therefore, the studies were based on an unknown mechanism of reaction and potentially a high background. To solve these problems, one of the most important things is to find a more suitable substrate for assay of the enzyme. We developed an assay strategy for determining the substrate for denitrase combining 2D-gel electrophoresis and an on-blot enzyme assay. The resulting substrate from RAW 264.7 cells was Histone H1.2, an isoform protein of linker histone. Histone H1.2 has only one tyrosine residue in the entire molecule, which ensures the exact position of the substrate to be involved. It has been reported that Histories are the most prominent nitrated proteins in cancer tissues. It was also demonstrated that tyrosine nitration of Histone H1 occurs in vivo. These findings lead us to the idea that Histone H1.2 might be an intrinsic substrate for denitrase. We nitrated recombinant and purified Histone H1.2 chemically and subjected it to an on-blot enzyme assay to characterize the activity. Denitrase activity behaved as an enzymatic activity because the reaction was time dependent and was destroyed by heat or trypsin treatment. The activity was shown to be specific for Histone H1.2, to differ from proteasome activity, and to require no additional cofactors.

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  • Nitration of PPAR gamma inhibits ligand-dependent translocation into the nucleus in a macrophage-like cell line, RAW 264 査読

    A Shibuya, K Wada, A Nakajima, M Saeki, K Katayama, T Mayumi, T Kadowaki, H Niwa, Y Kamisaki

    FEBS LETTERS   525 ( 1-3 )   43 - 47   2002年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Nitration of tyrosine residues in proteins has been observed in many inflammatory tissues of arthritis, ulcerative colitis, septic shock and ischemia-reperfusion injury. Although several studies have been carried out, it is still unclear what type of protein is nitrated and whether tyrosine nitration interferes with protein function. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor whose activation is linked to several physiological pathways including regulation of insulin sensitivity and control of inflammation. PPARgamma possesses several tyrosine residues, which might be potential targets for nitration by peroxynitrite during inflammatory responses. Here we have investigated whether PPARgamma is nitrated in macrophage-like RAW 264 cells and the effect of nitration on the translocation of PPARgamma into the nucleus. Western blot analysis showed that tumor necrosis factor-alpha, lipopolysaccharide or peroxynitrite treatment significantly increases the nitration of PPARgamma. Cell fractionation analysis and immunofluorescence coupled with confocal laser microscopy revealed that nitration of PPARgamma inhibits its ligand-dependent translocation from the cytosol into the nucleus. Together, these results indicate that nitration of PPARgamma during inflammation may be involved in a reduction in the control of inflammatory responses and also in the development of resistance to PPARgamma ligand-based therapies against inflammation. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

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  • Vanadate protects human neuroblastoma SH-SY5Y cells against peroxynitrite-induced cell death 査読

    M Saeki, S Maeda, Y Kamisaki

    JOURNAL OF CELLULAR BIOCHEMISTRY   85 ( 4 )   721 - 727   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    We investigated the effect of vanadate, a tyrosine phosphatase inhibitor, on cell death induced by peroxynitrite in human neuroblastoma SH-SY5Y cells. Vanadate prevented cell death induced by 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor; whereas SIN-1-induced cell death was not prevented by neither okadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, nor cyclosporin A, an inhibitor of serine/threonine phosphatase 2B. Vanadate did not prevent cell death induced by N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine, a nitric oxide donor. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), did not block the protective effect of vanadate, suggesting that the protective effect of vanadate is independent on PI3-kinase. Vanadate increased tyrosine phosphorylation of several proteins including the focal adhesion protein p130 Crk-associated substrate (p130(cas)). By the treatment with SIN-1, the endogenous association of p130(cas) and Crk was disrupted, and the association was restored by vanadate treatment. These results suggest that disruption of tyrosine phosphorylation signaling may be critical for peroxynitrite-induced cell death, and that vanadate prevents cell death at least in part through the enhancement in tyrosine phosphorylation of the proteins including p130(cas).

    DOI: 10.1002/jcb.10180

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  • Insulin-like growth factor-1 protects peroxynitrite-induced cell death by preventing cytochrome c-induced caspase-3 activation 査読

    M Saeki, S Maeda, K Wada, Y Kamisaki

    JOURNAL OF CELLULAR BIOCHEMISTRY   84 ( 4 )   708 - 716   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    We investigated the effect of lGF-1 on cell death induced by peroxynitrite in human neuroblastoma SH-SY5Y cells. Exposure of the cells to 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, caused cytochrome c release from the mitochondria, caspase-3-like activation, and cell death. Pre-incubation of the cells with the caspase-3 inhibitor partially prevented SIN-1-induced cell death. Simultaneous addition of IGF-1 reduced SIN-1-induced caspase3-like activation and cell death, whereas IGF-1 failed to reduce the release of cytochrome c. IGF-1 increased Akt phosphorylation, and Akt phosphorylation was inhibited by wortmannin, an inhibitor of phosphatidylinositol 3-kinase. In addition, wortmannin prevented IGF-1-evoked inhibition of cell death and caspase-3-like activation. in a cell-free system, addition of cytochrome c to cytosolic fraction resulted in caspase-3-like activation. The activation was reduced when the cytosolic fraction prepared from IGF-1-treated cells was used. These results suggest that IGF-1 protects peroxynitrite-induced cell death downstream of cytochrome c release through the inhibition of caspase-3-like activation. (C) 2002 Wiley-Liss, Inc.

    DOI: 10.1002/jcb.10086

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MISC

  • Reptinは胎仔上皮におけるDNA損傷応答を介して器官形成を制御する

    目黒史也, 目黒史也, 目黒史也, 柿原嘉人, 川崎真依子, 川崎勝盛, 川崎勝盛, 丹原惇, 丹原惇, トゥラカナン スッパラック, 工藤武久, 工藤武久, 山田茜, 山田茜, 前田健康, 多部田康一, 佐伯万騎男, 大峡淳

    新潟歯学会雑誌   50 ( 2 )   2020年

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  • 日本酒によるストレス誘発性の咬筋侵害応答の軽減効果は日本酒含有エタノールの直接作用ではない

    中谷 暢佑, 柿原 嘉人, 清水 志保, 黒瀬 雅之, 佐伯 万騎男, 高木 律男, 山村 健介, 岡本 圭一郎

    Journal of Oral Biosciences Supplement   2018   260 - 260   2018年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ROCK阻害剤の骨代謝および矯正学的歯の移動への影響

    中田 樹里, 柿原 嘉人, 秋葉 陽介, 江口 香里, 丹原 惇, 大倉 麻里子, 加藤 寛子, 泉 健次, 佐伯 万騎男, 齋藤 功

    新潟歯学会雑誌   47 ( 2 )   120 - 120   2017年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • ROCK阻害剤による骨形成促進メカニズムの解析

    中田 樹里, 柿原 嘉人, 丹原 惇, 佐伯 万騎男, 齋藤 功

    日本矯正歯科学会大会プログラム・抄録集   76回   184 - 184   2017年10月

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    記述言語:日本語   出版者・発行元:(公社)日本矯正歯科学会  

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  • 分子シャペロンR2TPの口腔扁平上皮癌進展における作用機序の解析

    木口 哲郎, 柿原 嘉人, 山崎 学, 高木 律男, 佐伯 万騎男

    Journal of Oral Biosciences Supplement   2017   256 - 256   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • セロトニン再取り込み阻害薬は繰り返しストレスによる咬筋の侵害受容反応の増強を抑制する

    中谷 暢佑, 黒瀬 雅之, 清水 志保, 柿原 嘉人, 木口 哲郎, 長谷川 真奈, 佐伯 万騎男, 高木 律男, 山村 健介, 岡本 圭一郎

    Journal of Oral Biosciences Supplement   2017   463 - 463   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 『酒は百薬の長』の根拠を科学的に解明するストレス誘発性の咬筋侵害受容反応に対する日本酒の影響について

    岡本 圭一郎, 中谷 暢佑, 黒瀬 雅之, 柿原 嘉人, 木口 哲郎, 長谷川 真奈, 藤井 規孝, 佐伯 万騎男, 高木 律男, 山村 健介

    Journal of Oral Biosciences Supplement   2017   462 - 462   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • ROCK阻害剤の骨代謝への影響とその作用機序の解析

    中田 樹里, 秋葉 陽介, 江口 香里, 丹原 惇, 齋藤 功, 柿原 嘉人, 佐伯 万騎男

    日本骨代謝学会学術集会プログラム抄録集   35回   184 - 184   2017年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨代謝学会  

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  • 破骨細胞分化に影響を与える薬剤のスクリーニングとその作用機序の解析

    中田 樹里, 柿原 嘉人, 秋葉 陽介, 丹原 惇, 齋藤 功, 佐伯 万騎男

    日本骨代謝学会学術集会プログラム抄録集   34回   207 - 207   2016年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨代謝学会  

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  • リボソーム合成制御因子R2TPの口腔扁平上皮癌進展における作用機序の解析

    木口哲郎, 木口哲郎, 柿原嘉人, 山崎学, 永田昌毅, 高木律男, 佐伯万騎男

    日本薬理学会北部会プログラム・抄録集   67th   64   2016年

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    記述言語:日本語  

    J-GLOBAL

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  • 破骨細胞の分化を誘導する小分子化合物の探索

    西川 実沙, 柿原 嘉人, 秋葉 陽介, 江草 宏, 佐伯 万騎男

    Journal of Oral Biosciences Supplement   2015   546 - 546   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)歯科基礎医学会  

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  • 破骨細胞分化に影響を与える薬剤の探索

    中田 樹里, 柿原 嘉人, 丹原 惇, 齋藤 功, 江草 宏, 佐伯 万騎男

    日本骨代謝学会学術集会プログラム抄録集   33回   196 - 196   2015年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨代謝学会  

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  • 破骨細胞分化に影響を与える薬剤のケミカルライブラリースクリーニング

    中田樹里, 中田樹里, 柿原嘉人, 秋葉陽介, 丹原惇, 齋藤功, 江草宏, 佐伯万騎男

    日本薬理学会北部会プログラム・抄録集   66th   53   2015年

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    記述言語:日本語  

    J-GLOBAL

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  • 破骨細胞の分化を誘導する小分子化合物の探索

    西川実沙, 柿原嘉人, 秋葉陽介, 江草宏, 佐伯万騎男

    Journal of Oral Biosciences Supplement (Web)   2015   2015年

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  • PICK1 Regulates Osteoclastogenesis by Binding to Calcineurin B

    Yuya Kamano, Makio Saeki, Hiroshi Egusa, Hirofumi Yatani, Yoshinori Kamisaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   124   93P - 93P   2014年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Monad regulates stability of Amphiregulin mRNA

    Kyoko Kurioka, Makio Saeki, Yasuyuki Irie, Yoshinori Kamisaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   118   213P - 213P   2012年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Molecular cloning of novel Monad binding protein containing tetratricopeptide repeat domains

    Yuki Itsuki, Makio Saeki, Hirokazu Nakahara, Hiroshi Egusa, Yasuyuki Irie, Yutaka Terao, Shigetada Kawabata, Hirofumi Yatani, Yoshinori Kamisaki

    FEBS LETTERS   582 ( 16 )   2365 - 2370   2008年7月

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    記述言語:英語   出版者・発行元:WILEY  

    We have previously reported that Monad, a novel WD40 repeat protein, potentiates apoptosis induced by tumor necrosis factor-alpha(TNF-alpha) and cycloheximide (CHX). By affinity purification and mass spectrometry, we identified RNA polymerase II-associated protein 3 ( RPAP3) as a binding protein of Monad. Overexpression of RPAP3 in HEK 293 potentiated caspase-3 activation and apoptosis induced by TNF-alpha and CHX. In addition, knockdown of RPAP3 by RNA interference resulted in a significant reduction of apoptosis induced by TNF-alpha and CHX in HEK293 and HeLa cells. These results raise the possibility that RPAP3, together with Monad, may function as a novel modulator of apoptosis pathway.

    DOI: 10.1016/j.febslet.2008.05.041

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  • Involvement of calcineurin in osteoclastogenesis mediated by RANKL

    Tsutomu Iida, Hiroshi Egusa, Makio Saeki, Masanori Doi, Hirofumi Yatani, Yoshinori Kamisaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   154P - 154P   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Molecular cloning and characterization of Monad binding protein 1 containing tetratricopeptide repeat domain

    Yuki Itsuki, Makio Saeki, Yasuyuki Irie, Ko Okamura, Hirohumi Yatani, Yoshinori Kamisaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   110P - 110P   2007年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • The role of calcineurin in osteoclastogenesis mediated by RANKL

    Tsutomu Iida, Hiroshi Egusa, Makio Saeki, Masanori Doi, Yuki Itsuki, Hirifumi Yatani, Yoshinori Kamisaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   164P - 164P   2007年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Inhibition by nifedipine of adherence- and activated macrophage-induced death of human gingival fibroblasts

    Y Fujimori, S Maeda, M Saeki, Morisaki, I, Y Kamisaki

    EUROPEAN JOURNAL OF PHARMACOLOGY   415 ( 1 )   95 - 103   2001年3月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    The effects of nifedipine on the death and proliferation of gingival fibroblasts were investigated to elucidate the mechanism of gingival overgrowth that is associated with chronic administration of Ca2+ channel blockers. The number of adhered viable and dead fibroblasts obtained from healthy human gingiva increased after confluence, whereas cell death was inhibited by nifedipine in a concentration-dependent manner. A similar inhibition was also observed in the presence of other calcium channel blockers, such as nicardipine, diltiazem, and verapamil. When gingival fibroblasts were co-cultured with RAW264 (macrophage-like) cells, lipopolysaccharide (LPS) caused the concentration-dependent death of fibroblasts. Nifedipine significantly inhibited the LPS-induced cell death. Although neither LPS nor N-ethyl-2-(1-ethyl-2-hydroxy-2-nitroso-hydrazino)-ethanamine, a nitric oxide donor, directly caused fibroblast death, 3-morpholino-sydnonimine (SIN-1). a peroxynitrite donor, induced fibroblast death, regardless of the presence of RAW cells. The cell death induced by SIN-1 was not affected by nifedipine treatment. LPS stimulation caused an increase in the immunoreactivity of inducible nitric oxide synthase (iNOS) and in the nitrite concentration in the incubation medium of RAW cells. The induction of iNOS was completely prevented by the incubation with nifedipine. The inhibition by nifedipine of nitrite production in RAW cells was also observed after treatment with nicardipine, but not with either diltiazem or verapamil. Therefore, the inhibition by nifedipine of both adherence- and LPS-stimulated macrophage-induced death of fibroblasts may be the mechanism of gingival overgrowth seen during chronic treatment with Ca2+ channel blockers. (C) 2001 Published by Elsevier Science B.V.

    DOI: 10.1016/S0014-2999(01)00810-X

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  • Involvement of mitogen-activated protein kinase in peroxynitrite-induced cell death of human neuroblastoma SH-SY5Y cells

    M Saeki, Y Kamisaki, S Maeda

    NEUROSCIENCE RESEARCH   38 ( 2 )   213 - 216   2000年10月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We have investigated the activation of mitogen-activated protein kinase (MAP kinase) in relation to cell death induced by peroxynitrite in human neuroblastoma SH-SY5Y cells. Exposure of the cells to peroxynitrite caused transient increase in MAP kinase activity, and resulted in cell death. PD98059, a selective inhibitor of MAP kinase kinase, reduced peroxynitrite-induced cell death. These results suggest that the activation of MAP kinase may be involved in cell death induced by peroxynitrite. (C) 2000 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(00)00138-3

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  • Potentiation of carbachol-induced Ca2+ release by peroxynitrite in human neuroblastoma SH-SY5Y cells

    M Saeki, Y Kamisaki, S Maeda

    NEUROCHEMICAL RESEARCH   25 ( 7 )   909 - 914   2000年7月

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    記述言語:英語   出版者・発行元:KLUWER ACADEMIC/PLENUM PUBL  

    We have investigated the effect of 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, on carbachol-induced increase in intracellular Ca2+ concentration ([Ca2+](i)) in human neuroblastoma SH-SY5Y cells by means of single cell imaging of [Ca2+](i). SIN-1 potentiated carbachol-induced [Ca2+](i) rise regardless of external Ca2+, and the potentiation was completely inhibited by super oxide dismutase, indicating that peroxynitrite may enhance Ca2+ release from intracellular stores. On the other hand, SIN-1 reduced carbachol-induced inositol 1,4,5-trisphosphate (IP3) formation. Genistein, a tyrosine kinase inhibitor, potentiated carbachol-induced rise of [Ca2+](i) regardless of external Ca2+. These results suggest that peroxynitrite may potentiate the release of Ca2+ from intracellular stores through the perturbation of regulation in tyrosine phosphorylation-dephosphorylation system.

    DOI: 10.1023/A:1007540005737

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  • Morphine prevents peroxynitrite-induced death of human neuroblastoma SH-SY5Y cells through a direct scavenging action

    T Kanesaki, M Saeki, Y Ooi, M Suematsu, K Matsumoto, M Sakuda, K Saito, S Maeda

    EUROPEAN JOURNAL OF PHARMACOLOGY   372 ( 3 )   319 - 324   1999年5月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    N-Ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12), a nitric oxide donor, 3-morpholinosydnonimine (SIN-1), a generator of peroxynitrite (ONOO-), and peroxynitrite induced cell death accompanied by DNA fragmentation in human neuroblastoma SH-SY5Y cell cultures. Morphine prevented the cell death induced by SIN-1 or peroxynitrite, but not that induced by NOC12. The protective effect of morphine was concentration-dependent (10-100 mu M), but was not antagonized by naloxone. The selective ligands for opioid receptor subtypes, [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]enkephalin (DAMGO, mu-opioid receptor agonist), [D-Pen(2,5)]enkephalin (DPDPE, delta-opioid receptor agonist) and trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benzeneacetamide (U-50488, kappa-opioid receptor agonist) even at the concentration of 100 mu M did not prevent the cell death induced by SIN-1. From measurement of the absorbance spectrum of peroxynitrite, the decomposition of peroxynitrite in 0.25 M potassium phosphate buffer (pH 7.4) was Very rapid and complete within seconds. However, the absorbance was very stable in the presence of morphine. In addition, morphine inhibited peroxynitrite-induced nitration of tyrosine in a concentration-dependent manner. These results indicate that morphine rapidly reacts with peroxynitrite. The present study showed that morphine prevented peroxynitrite-induced cell death through its direct scavenging action, suggesting that morphine can protect cells against damage caused by peroxynitrite. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0014-2999(99)00206-X

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  • p130(cas) is a cellular target protein for tyrosine nitration induced by peroxynitrite

    M Saeki, S Maeda

    NEUROSCIENCE RESEARCH   33 ( 4 )   325 - 328   1999年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We found that the exposure of human neuroblastoma SH-SY5Y cells to the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) induced tyrosine nitration of a 130-kDa protein, and prevented tyrosine phosphorylation of the 130-kDa protein. The focal adhesion protein p130(cas) was identified as a component of the 130-kDa protein using specific antibody. These results suggest that p130(cas) is a new target protein for nitration induced by SIN-1. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0168-0102(99)00019-X

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  • Effect of morphine on secretion of amylase from isolated parotid acini

    Y Miwa, M Saeki, A Yamaji, S Maeda, K Saito

    LIFE SCIENCES   59 ( 21 )   1809 - 1819   1996年10月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The effect of morphine on amylase secretion was studied in isolated rat parotid acinar cells. It was found that aluminum fluoride (AlCl3/NaF) and dibutyryl-cyclic AMP but not by cyclic AMP, enhanced amylase secretion. Cyclic AMP was effective in enhancing secretion following permeabilization of cells with alpha-toxin. Following treatment of cells with alpha-toxin, both GTP and GTP-gamma-S also enhanced secretion. Morphine reduced AlCl3/NaF- or GTP-induced secretion of amylase, but was without effect on GTP-gamma-S-induced secretion. Photoaffinity labeling by the use of [P-32] 4-azidoanilido GTP revealed its incorporation into 43 kDa and 31 kDa proteins. Incorporation was further enhanced with AlCl3/NaF. Morphine reduced labeling of the 43 kDa protein. Immunoblot analysis identified the 43 kDa GTP binding protein as Gs. When [gamma(32)P] GTP was preloaded into permeabilized acinar cells and its hydrolysis measured, morphine stimulated and AlCl3/NaF inhibited GTPase activity. These results suggested the involvement of Gs in secretion of amylase. Furthermore, morphine reduced secretion of amylase by stimulating GTPase activity and by reducing the incorporation of GTP into Gs.

    DOI: 10.1016/0024-3205(96)00524-3

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共同研究・競争的資金等の研究

  • 難治性口腔扁平上皮癌におけるセツキシマブ耐性ループ仮説の検証

    2018年 - 2020年

    基盤C 

    佐伯 万騎男

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    担当区分:研究代表者  資金種別:競争的資金

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  • [急がば回れ」の骨再生:骨吸収促進薬を用いた新規骨疾患治療薬の探索

    挑戦的萌芽 

    佐伯 万騎男

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    担当区分:研究代表者  資金種別:競争的資金

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  • 歯科薬理学特論ⅡA

    2017年
    機関名:新潟大学

  • 早期臨床実習Ⅱ

    2015年
    -
    現在
    機関名:新潟大学

  • 「食べる」

    2015年
    -
    現在
    機関名:新潟大学

  • 疾病とその病態

    2015年
    -
    現在
    機関名:新潟大学

  • 選択実習Ⅰc

    2015年
    -
    2017年
    機関名:新潟大学

  • 基礎科学演習

    2015年
    -
    2016年
    機関名:新潟大学

  • 薬理学

    2014年
    -
    現在
    機関名:新潟大学

  • 組織工学実習

    2014年
    -
    2016年
    機関名:新潟大学

▶ 全件表示