Channel-mediated mechanisms of induction of and protection against cell death

• Project/Area Number: 17209006
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: OKADA Yasunobu National Institute for Physiological Sciences, 所長 (10025661)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Takahiro 生理学研究所, 細胞器官研究系, 助手 (40353437) ; TAKAHASHI Nobuyuki 京都大学, 農学研究科, 助教 (50370135) ; INOUE Hana 生理学研究所, 細胞器官研究系, 特任助手 (20390700) ; URAMOTO Hiromi 生理学研究所, 細胞器官研究系, 特別協力研究員 (50390696) ; NUMATA Tomohiro 京都大学, 工学研究科, 助教 (20455223)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥49,140,000 (Direct Cost: ¥37,800,000、Indirect Cost: ¥11,340,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000); Fiscal Year 2006: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000); Fiscal Year 2005: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
• Keywords: アポトーシス / ネクローシス / 虚血 / アニオンチャネル / カチオンチャネル / 細胞容積調節 / 抗癌剤耐性 / 心筋梗塞 / キナーゼ / 細胞死 / チャネル / 生理学 / 活性酸素種 / 心筋細胞 / ニューロン / 癌細胞

Research Abstract

アポトーシス時において見られる細胞縮小(Apoptotic Volume Decrease : AVD)の誘導は、容積感受性外向整流性アニオンチャネル(VSOR)とK+チャネルの活性化によるKClの細胞外流出によってもたらされる。今回、類上皮癌細胞の抗癌剤シスプラチンによるアポトーシス死についてもこれは同様であること、そしてシスプラチン耐性を獲得した本細胞の亜株においては両チャネル活性が欠失することを明らかにした。また、高浸透圧活性化カチオンチャネル(HICC)は、細胞縮小後の容積調節をもたらして、アポトーシス死に対して救済的に働くことを見出した。ネクローシス時に見られる細胞膨張(Necrotic Volume Increase : NVI)の誘導はNaClの細胞内流入によってもたらされるが、酸毒性やアンモニア毒性時におけるNa+流入にはTRPM7やTRPM2カチオンチャネルが、過興奮毒性時におけるCl-流入にはVSORアニオンチャネルが関与することを明らかにした。虚血・再灌流性の心筋細胞や海馬ニューロンのアポトーシスの誘導にはVSOR活性化が関与し、心筋梗塞下の心筋細胞ネクローシス死に対してはCFTRアニオンチャネルが防御的に働くことを明らかにした。

Research Products

• [Journal Article] Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel. (2009)
  • Author(s): Y. Okada, K. Sato & T. Numata
  • Journal Title: J. Physiol. (London) 587 Pages: 2141-2149
  • Peer Reviewed
• [Journal Article] The maxi-anion channel : a classical channel playing novel roles through an unidentified molecular entity (2009)
  • Author(s): Ravshan Z. Sabirov
  • Journal Title: Journal of Physiological Sciences 59 Pages: 3-21
  • Peer Reviewed
• [Journal Article] Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel (2009)
  • Author(s): Yasunobu Okada
  • Journal Title: Journal of Physiology (London)
  • Peer Reviewed
• [Journal Article] Hypertonicity-induced cation channels rescue cells from staurosporine-elicited apoptosis. (2008)
  • Author(s): T. Numata, K. Sato, Y. Okada & F. Wehner
  • Journal Title: Apoptosis 13 Pages: 895-903
  • Peer Reviewed
• [Journal Article] Hypertonicity-induced cation channels rescue cells from staurosporine-elicited apoptosis (2008)
  • Author(s): Tomohiro Numata
  • Journal Title: Apoptosis 13 Pages: 895-903
  • Peer Reviewed
• [Journal Article] Volume-sensitive Cl^- channel as a regulator of acquired cisplatin resistance (2008)
  • Author(s): Takahiro Shimizu
  • Journal Title: Anticancer Research 28 Pages: 75-84
  • Peer Reviewed
• [Journal Article] Oxygen-glucose deprivation induces ATP release via maxi-anion channels in astrocytes (2008)
  • Author(s): Hong-Tao Liu
  • Journal Title: Purinergic Signalling 4 Pages: 147-154
  • Peer Reviewed
• [Journal Article] Anion channel blockers attenuate delayed neuronal cell death induced by transient forebrain ischemia. (2007)
  • Author(s): H. Inoue, H. Ohtaki, T. Nakamachi, S. Shioda & Y. Okada
  • Journal Title: J. Neurosci. Res. 85 Pages: 1427-1435
  • Peer Reviewed
• [Journal Article] Role of volume-sensitive chloride channel in excitotoxic neuronal injury. (2007)
  • Author(s): H. Inoue & Y. Okada
  • Journal Title: J. Neurosci 27 Pages: 1445-1455
  • Peer Reviewed
• [Journal Article] Impaired activity of volume-sensitive Cl- channel is involved in cisplatin resistance of cancer cells. (2007)
  • Author(s): E.L. Lee, T. Shimizu, T. Ise, T. Numata, K. Kohno & Y. Okada
  • Journal Title: J. Cell. Physiol 211 Pages: 513-521
  • Peer Reviewed
• [Journal Article] Signalling events employed in the hypertonic activation of cation channels in HeLa cells (2007)
  • Author(s): Frank Wehner
  • Journal Title: Cellular Physiology and Biochemistry 20 Pages: 75-82
  • Peer Reviewed
• [Journal Article] Role of acid-sensitive outwardly rectifying anion channels inacidosis-induced cell death in human epithelial cells (2007)
  • Author(s): Hai-Yan Wang
  • Journal Title: Pfliugers Archiv European Journal of Physiology 454 Pages: 223-233
  • Peer Reviewed
• [Journal Article] Prerequisite role of persistent cell shrinkage in apoptosis of human epithelial cells (2007)
  • Author(s): Takahiro Shimizu
  • Journal Title: Acta Physiologica Sinica 59 Pages: 512-526
  • Peer Reviewed
• [Journal Article] Anion channel blockers attenuate delayed neuronal cell death induced by transient forebrain ischemia. (2007)
  • Author(s): H.Inoue
  • Journal Title: J. Neurosci. Res. (印刷中)
• [Journal Article] Role of volume-sensitive chloride channel in excitotoxic neuronal injury. (2007)
  • Author(s): H.Inoue
  • Journal Title: J. Neurosci 27 Pages: 1445-1455
• [Journal Article] Impaired activity of volume-sensitive Cl^- channel is involved in cisplatin resistance of cancer cells. (2007)
  • Author(s): E.L.Lee
  • Journal Title: J. Cell. Physiol. 211 Pages: 513-521
• [Journal Article] Dysfunction of regulatory volume increase is a key component of apoptosis. (2007)
  • Author(s): E.Maeno
  • Journal Title: FEBS Lett. 580 Pages: 6513-6517
• [Journal Article] Normotonic cell shrinkage induced by Na^+ deprivation results in apoptotic cell death in human epithelial HeLa cells. (2006)
  • Author(s): M.Nukui
  • Journal Title: J. Physiol. Sci. 56 Pages: 335-339
• [Journal Article] Normotonic cell shrinkage induces apoptosis under extracellular low Cl^- conditions in human lymphoid and epithelial cells. (2006)
  • Author(s): E.Maeno
  • Journal Title: Acta Physiologica 187 Pages: 217-222
• [Journal Article] Roles of volume-sensitive Cl^- channel in cisplatin-induced apoptosis in human epidermoid cancer cells. (2005)
  • Author(s): T.Ise
  • Journal Title: J.Membrane Biol. 205 Pages: 139-145
• [Journal Article] Chloride channel inhibition prevents ROS-dependent apoptosis induced by ischemia-reperfusion in mouse cardiomyocytes. (2005)
  • Author(s): X.Wang
  • Journal Title: Cell.Physiol.Biochem. 16 Pages: 147-154
• [Journal Article] Volume-sensitive chloride channels in mouse cortical neurons : characterization and role in volume regulation. (2005)
  • Author(s): H.Inoue
  • Journal Title: Eur.J.Neurosci. 21 Pages: 1648-1658
• [Journal Article] ClC-3-independent sensitivity of apoptosis to Cl^- channel blockers in mouse cardiomyocytes. (2005)
  • Author(s): N.Takahashi
  • Journal Title: Cell.Physiol.Biochem. 15 Pages: 263-270
• [Journal Article] HCO_3-independent rescue from apoptosis by stilbene derivatives in at cardiomyocytes. (2005)
  • Author(s): S.Tanabe
  • Journal Title: FEBS Lett. 579 Pages: 517-522
• [Journal Article] ATP release via anion channels. (2005)
  • Author(s): R.Z.Sabirov
  • Journal Title: Purinergic Signalling 1 Pages: 311-328
• [Presentation] Physiology and puzzles of the volume-sensitive anion channel (2008)
  • Author(s): Yasunobu Okada
  • Organizer: Journal of Physiology Symposium "Chloride channels : insight into function from human disease"
  • Place of Presentation: Beijing, China
  • Year and Date: 2008-10-18
• [Presentation] メカノセンサーとしてのTRPM7チャネルとその生理的役割 (2008)
  • Author(s): 沼田 朋大
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-25
• [Presentation] Rescue of apoptosis by activation of hypertonicity-induced cation channels in human epithelial cells. J. Physiol. Sci. 58 (Suppl) S209 (2008)
  • Author(s): Y. Okada, F. Wehner, T. Numata
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] 酸感受性外向整流性クロライドチャネルの温度感受性とその役割 (2007)
  • Author(s): 沼田 朋大
  • Organizer: 第54回中部日本生理学会第100回近畿生理学
  • Place of Presentation: 津、三重
  • Year and Date: 2007-10-19
• [Presentation] Hypertonicity-induced cation channels rescue HeLa cells from taurosporine-induced apoptosis (2007)
  • Author(s): Tomohiro Numata
  • Organizer: 6th International Symposium on Cell Volume Regulation in Health and Disease
  • Place of Presentation: Salzburg,Austria
  • Year and Date: 2007-09-23
• [Presentation] Protection of cardiomyocytes from ischemic injury by activation of CFTR Cl^- channel (2007)
  • Author(s): Hiromi Uramoto
  • Organizer: 6th International Symposium on Cell Volume Regulation in Health and Disease
  • Place of Presentation: Salzburg,Austria
  • Year and Date: 2007-09-23
• [Presentation] Activation of volume-sensitive anion channel is involved in induction of both necrotic and apoptotic death in brain neurons (2007)
  • Author(s): Yasunobu Okada
  • Organizer: 6th International Symposium on Cell Volume Regulation in Health and Disease
  • Place of Presentation: Salzburg,Austria
  • Year and Date: 2007-09-22
• [Presentation] Reciprocal regulation of regulatory volume increase (RVI) by Akt and ASK. Abstract p112 (2007)
  • Author(s): N. Takahashi, M. Subramanyan, Y. Hasegawa & Y. Okada
  • Organizer: 6th International Symposium on Cell Volume Regulation in Health and Disease
  • Place of Presentation: Salzburg, Austria
• [Presentation] Protection of cardiomyocytes from ischemic injury by activation of CFTR Cl- channel. Abstract p103 (2007)
  • Author(s): H. Uramoto, N. Takahashi & Y. Okada
  • Organizer: 6th International Symposium on Cell Volume Regulation in Health and Disease
  • Place of Presentation: Salzburg, Austria
• [Presentation] Physiology in Cell Death Induction : Roles of Anion Channels and Disordered Cell Volume Regulation. J. Physiol. Sci. 57 (Suppl) S2 (2007)
  • Author(s): Y. Okada
  • Organizer: 第84回日本生理学会大会、田崎記念レクチャー
  • Place of Presentation: 大阪
• [Presentation] Volume-sensitive chloride channel involved in necrotic neuronal death by excitotoxicity. J. Physiol. Sci. 56 (Suppl) S113 (2006)
  • Author(s): H. Inoue, Y. Okada
  • Organizer: 第83回日本生理学会大会
  • Place of Presentation: 前橋
• [Book] Cell volume-sensitive chloride channel : Phenotypic properties and molecular identity. In, "Mechanisms and Significance of Cell Volume Regulation" (ed. F. Lang), pp 9-24 (2006)
  • Author(s): Y. Okada
  • Publisher: Karger, Basel
• [Book] Cell volume-sensitive chloride channel : Phenotypic properties and molecular identity. In, "Mechanisms and Significance of Cell Volume Regulation" (ed. F. Lang) (2006)
  • Author(s): Y.Okada
  • Total Pages: 16
  • Publisher: Karger
• [Book] Essential role of anion channel in induction of apoptotic and necrotic cell death. In, "Ion Channels in the Pulmonary Vasculature" (ed. J. X.-J. Yuan), pp 527-544 (2005)
  • Author(s): Y. Okada, E. Maeno, T. Nabekura & S. Mori
  • Publisher: Taylor & Francis : Boca Raton, FL
• [Book] Essential role of anion channel in induction of apoptotic and necrotic cell death. In, "Ion Channels in the Pulmonary Vasculature" (2005)
  • Author(s): Y.Okada
  • Total Pages: 18
  • Publisher: Taylor & Francis
• [Remarks] 生理学研究所 細胞器官研究系 機能協関研究部門webページ
  • URL: http://www.nips.ac.jp/rvd/
• [Remarks] 生理学研究所細胞器官研究系機能協関研究部門webページ
  • URL: http://www.nips.ac.jp/rvd/