Integrated study of cell death: Biology focusing on multiple mechanisms of mammalian cell death

2012 Fiscal Year Final Research Report

• Project/Area Number: 19GS0316
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• Research Institution: Osaka University
• Principal Investigator: TSUJIMOTO Yoshihide 大阪大学, 医学系研究科, 教授 (70132735)
• Co-Investigator(Kenkyū-buntansha): EGUCHI Yutaka 大阪大学, 大学院・医学系研究科, 准教授 (20243214) ; SHINZAWA Koei 大阪大学, 大学院・医学系研究科, 助教 (70403186) ; SHIBUYA Toshiharu 大阪大学, 大学院・医学系研究科, 助教 (70448033) ; HAMADA Yoshio 基礎生物学研究所, 細胞社会学, 助教 (10132739)
• Project Period (FY): 2007 – 2012
• Keywords: 細胞死 / アポトーシス / ネクローシス / プログラム細胞死 / オートファジー

Research Abstract

Based on our hypothesis that non-apoptotic cell death mechanisms play an important role in physiological programmed death in addition to pathological death, we have performed detailed studies and discovered that non-apoptotic death mechanisms play the major role in programmed death involved in turn over of mouse small intestinal epithelial cells, placenta formation, and bone formation as well as in pathological death of neurons in INAD model mouse withmutations in PLA2G6 gene. This implies that cell death research needs the paradigm shift. We have also found some chemical inhibitors or genes for theabove-mentioned non-apoptotic programmed death and for non-apoptotic death,which we observed in cultured cells, providing the firm basis for the next generation of cell death research.

Research Products

• [Journal Article] Deleterious effects of mitochondrial ROS generated by KillerRed photodynamic action in human cell lines and C. elegans (2012)
  • Author(s): Shibuya, T. and Tsujimoto, Y.
  • Journal Title: J. Photochem. Photobiol. Biol Volume: 117 Pages: 1-12
• [Journal Article] Multiple ways to die: Non-apoptotic forms of cell death. (2012)
  • Author(s): Tsujimoto, Y.
  • Journal Title: Acta Oncol. Volume: 51 Pages: 293-300
• [Journal Article] Analysis of two major intracellular phospholipase A2s in mast cells reveals crucial contribution of cPLA2{alpha}, not iPLA2{beta}, to lipid mobilization in proximal mast cells and distal fibroblasts (2011)
  • Author(s): Ueno, N., Taketomi, Y., Yamamoto, K., Hirabayashi, T., Kamei, D., Kita, Y., Shimizu, T., Shinzawa, K., Tsujimoto, Y., Ikeda, K., Taguchi, R., and Murakami, M.
  • Journal Title: J Biol Chem. Volume: 286 Pages: 37249-37263
• [Journal Article] Insufficient remodeling of membranes of mitochondria and axon terminals causes neuroaxonal dystrophy in calcium-independent phospholipase A2β deficiency (2011)
  • Author(s): Beck, G., Sugiura, Y., Shinzawa, K., Kato, S., Setou, M., Tsujimoto, Y., Sakoda, S., and Sumi-Akamaru, H
  • Journal Title: J. Neurosci. Volume: 31 Pages: 11411-11420
• [Journal Article] corticosterone which is associated with thymic atrophy in mice. (2011)
  • Author(s): Youn, D.-Y., Yoon, J.-S., Kim, Y.K., Yeum, C.E., Lee, S.-B., Youn, H.-J., Tsujimoto, Y. and Lee, J.-H.
  • Journal Title: me. J. Physiol. Endocrinology and Metabolism Volume: 301 Pages: E223-231
• [Journal Article] Delayed-onset caspase-dependent massive hepatocyte apoptosis upon Fas activation in Bak/Bax-deficient mice (2011)
  • Author(s): Hikita, H., Takehara, T., Kodama, T., Shimizu, S., Shigekawa, M., Hosui, A., Miyagi, T., Tatsumi, T., Ishida, H., Li, W., Kanto, T., Hiramatsu, N., Shimizu, S., Tsujimoto, Y. and Hayashi, N.
  • Journal Title: Hepatology Volume: 54 Pages: 240-251
• [Journal Article] Screening of cell death genes with a mammalian genome-wide RNAi library. (2010)
  • Author(s): Tsujii, H., Eguchi, Y., Chenchik, A., Mizutani, T., Yamada, K., and Tsujimoto, Y.
  • Journal Title: J. Biochem. Volume: 148 Pages: 157-170
• [Journal Article] Cyclophilin D-dependent mitochondrial permeability transition is not involved in neurodegeneration in mnd2 mutant mice. (2010)
  • Author(s): Ideguchi, K., Shimizu, S., Okumura, M. and Tsujimoto, Y.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 393 Pages: 264-267
• [Journal Article] Noxa is necessary for hydrogen peroxide-induced caspase-dependent cell death. (2010)
  • Author(s): Aikawa, T., Shinzawa, K., Tanaka, N. and Tsujimoto, Y.
  • Journal Title: FEBS Letter Volume: 584 Pages: 681-688
• [Journal Article] Involvement of JNK in the regulation of autophagic cell death (2010)
  • Author(s): Shimizu, S., Konishi, A., Nishida, Y., Mizuta, T., Nishina, H., Yamamoto, A. and Tsujimoto, Y.
  • Journal Title: Oncogene Volume: 29 Pages: 2070-2082
• [Journal Article] The role of cyclophilin D in learning and memory (2010)
  • Author(s): Mouri, A., Noda, Y., Shimizu, S., Tsujimoto, Y., and Nabeshima, T.
  • Journal Title: Hippocampus Volume: 20(2) Pages: 293-304
• [Journal Article] Discovery of ATG5/ATG7-independent alternate macroautophagy. (2009)
  • Author(s): Nishida , Y., Arakawa, S., Fujitani, K., Yamaguchi, H., Mizuta, T., Kanaseki, T., Komatsu, M., Otsu, K., Tsujimoto, Y. and Shimizu, S.
  • Journal Title: Nature Volume: 461 Pages: 654-658
• [Journal Article] Requirement of voltag e-dependent anion channel 2 for pro-apoptotic activity of Bax (2009)
  • Author(s): Yamagata, H., Shimizu, S., Nishida, Y., Watanabe, Y., Craigen, W. J. and Tsujimoto, Y.
  • Journal Title: Oncogene Volume: 28 Pages: 3563-3572
• [Journal Article] Essential role of p38 MAPK in caspase-independent, iPLA2-dependent cell death under hypoxia/low glucose conditions. (2009)
  • Author(s): Aoto, M., Shinzawa, K., Suzuki, Y., Ohkubo, N., Mitsuda, N. and Tsujimoto, Y.
  • Journal Title: FEBS letter Volume: 583 Pages: 1611-1618
• [Journal Article] hnRNP L binds to CA repeats in the 3` UTR of bcl-2 mRNA. (2009)
  • Author(s): Lee, D.-H., Lim, M.-H., Youn, D.-Y., Jung, S. E., Ahn, Y. S., Tsujimoto, Y. a n d Lee, J.-H.
  • Journal Title: Biochem. Biophys. Res. Comm. Volume: 382(3) Pages: 583-7
• [Journal Article] Bis deficiency results in early lethality with metabolic deterioration and involution of the spleen and thymus. (2008)
  • Author(s): Youn, D.-Y., Lee, D.-H., Lim, M.-H., Yoon, J.-S., Lim, J. H., Jung, S. E., Yeum, C. E., Park, C. W., Youn, H.-J., Lee, J.-S., Lee, S.-B., Ikawa, M., Okabe, M., Tsujimoto, Y. and Lee, J.-H
  • Journal Title: American J Physiol . Endocrinol. Metab Volume: 295 Pages: E1649-1357
• [Journal Article] Neuroaxonal dystrophy caused by group VIA phospholipase A2 deficiency in mice: a model of human neurodegenerative disease. (2008)
  • Author(s): Shinzawa, K., Sumi, H., Ikawa, M., Matsuoka, Y., Okabe, M., Sakoda, S. and Tsujimoto, Y.
  • Journal Title: J. Neurosci. Volume: 28 Pages: 2212-2220
• [Journal Article] Crystal structure of human cyclophilin D in complex with its inhibitor (2008)
  • Author(s): Kajitani, K., Fujihashi, M., Kobayashi, Y., Shimizu, S., Tsujimoto, Y. and Miki, K.
  • Journal Title: cyclosporin A at 0.96 A resolution. Proteins Volume: 70 Pages: 1635-1639
• [Journal Article] A Bax/Bak-independent mechanism of cytochrome c release (2007)
  • Author(s): Mizuta, K., Shimizu, S., Matsuoka, Y., Nakagawa, T. and Tsujimoto, Y.
  • Journal Title: J. Biol. Chem Volume: 282 Pages: 16623-16630
• [Presentation] Study of non-apoptotic programmed cell death during embryogenesis in mice by in vivo imaging (2012)
  • Author(s): 今川佑介、辻本賀英
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-13
• [Presentation] KillerRedにより産生されるミトコンドリア由来ROSのヒト培養細胞および線虫への影響 (2012)
  • Author(s): 渋谷利治、辻本賀英
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-12
• [Presentation] アセトアミノフェンにより誘導される接着肝細胞の同期的な細胞死 (2012)
  • Author(s): 斎藤千恵子、新沢康英、辻本賀英
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-12
• [Presentation] Necrostatin-1とDiindolyl-methaneで抑制される新規タイプのネクローシス (2011)
  • Author(s): 恵口豊、辻本賀英
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] 生体におけるプログラム細胞死 (2011)
  • Author(s): 辻本賀英
  • Organizer: 第43回日本臨床分子形態学会「招待講演(特別講演)」
  • Place of Presentation: 大阪医科大学
  • Year and Date: 2011-09-09
• [Presentation] マウス個体内で起こるプログラム細胞死 (2011)
  • Author(s): 辻本賀英
  • Organizer: 第20回日本Cell Death学会年会
  • Place of Presentation: 東京大学
  • Year and Date: 2011-07-29
• [Presentation] マウスにおけるプログラム細胞死 (2011)
  • Author(s): 辻本賀英
  • Organizer: 日本顕微鏡学会第67回学術講演会「招待講演」
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2011-05-16
• [Presentation] Cell death induced by mitochondrial ROS generated by photodynamic action of KillerRed protein (2010)
  • Author(s): 渋谷利治、辻本賀英
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-10
• [Presentation] Mechanism of enterocyte shedding from tips of mouse small intestinal villi (2010)
  • Author(s): 松岡洋祐、辻本賀英
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-10
• [Presentation] Role of non-apoptotic cell death during mouse placental vasculogenesis (2010)
  • Author(s): 浜田義雄、辻本賀英
  • Organizer: The 16th International Society of Differentiation Conference
  • Place of Presentation: 奈良新公会堂
  • Year and Date: 2010-11-15
• [Presentation] Programmed cell death in mouse: Multiple ways to die (2010)
  • Author(s): 辻本賀英
  • Organizer: Korean Society of Anatomy「招待講演」
  • Place of Presentation: Jeju Island(大韓民国)
  • Year and Date: 2010-10-14
• [Presentation] A role of non-apoptotic death in programmed cell death in mice (2010)
  • Author(s): 辻本賀英
  • Organizer: ECDO2011 Euroconference on Apoptosis「招待講演」
  • Place of Presentation: ストックホルムNorra Latin(スウェーデン)
  • Year and Date: 2010-09-17
• [Presentation] Study of cell death induced by photodynamic action of mitochondrial KillerRed protein (2010)
  • Author(s): 渋谷利治、辻本賀英
  • Organizer: Gordon Conference on Cell Death
  • Place of Presentation: Newport, RI(米国)
  • Year and Date: 2010-08-25
• [Presentation] iPLA2beta欠損マウスは神経軸索ジストロフィーを発症する (2010)
  • Author(s): 新沢康英、辻本賀英
  • Organizer: 第19回日本Cell Death学会年会
  • Place of Presentation: 愛知県産業労働会館
  • Year and Date: 2010-07-31
• [Presentation] マウスにおけるプログラム細胞死 (2010)
  • Author(s): 辻本賀英
  • Organizer: 第19回日本Cell Death学会年会
  • Place of Presentation: 愛知県産業労働会館
  • Year and Date: 2010-07-31
• [Presentation] Discovery of Atg5/Atg7 independent alternative macroautophagy and its molecular analysis (2009)
  • Author(s): 西田 友哉、荒川 聡子、辻本賀英、清水重臣
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] Bax依存的アポトーシスにおけるVDAC2の役割 (2008)
  • Author(s): 山形弘隆、清水重臣、渡辺義文、W. Craigen、辻本賀英
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-09
• [Presentation] 酸化ストレス誘導性アポトーシスの解析 (2008)
  • Author(s): 相川知徳、新沢康英、辻本賀英
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-09
• [Presentation] Roles of Bcl-2 in apoptosis and necrosis (2008)
  • Author(s): 辻本賀英
  • Organizer: International Euroconference "Mechanisms of Cell Death and Diseases: Advances in Therapeutic Intervention and Drug Development"「招待講演」
  • Place of Presentation: カスカイス(ポルトガル)
  • Year and Date: 2008-11-01
• [Presentation] The roles of Ca2+-indepenedent group VIA phospholipase A2 (iPLA2β) in hyopoxic death and neuroaxonal dystrophy. (2008)
  • Author(s): 新沢康英、隅 寿恵、松岡洋祐、佐古田三郎、辻本賀英
  • Organizer: The 7th International Cell Death Society Symposium Shanghai, China
  • Place of Presentation: 上海(中国)
  • Year and Date: 2008-06-08
• [Presentation] ストレス刺激で誘導されるグローバルヒストン脱アセチル化機構 (2007)
  • Author(s): 新沢康英、相川知徳、辻本賀英
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-18
• [Presentation] Multiple ways to die (2007)
  • Author(s): 辻本賀英
  • Organizer: The 19th Annual Meeting of the Korean Society for Molecular and Cellular B i o l o g y「招待講演」
  • Place of Presentation: ソウル(大韓民国)
  • Year and Date: 2007-06-19
• [Presentation] Multiple mechanisms of cell death and their regulation by Bcl-2 (2007)
  • Author(s): 辻本賀英
  • Organizer: Beijing Symposium "Cell Signaling in Cancer, Development and Stem Cells"「招待講演」
  • Place of Presentation: 北京(中国)
  • Year and Date: 2007-06-14
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/gene/www/index.html