Molecular elucidation and medical significance of redox-sensitive TRP channels in inflammatory cell infiltration.

2011 Fiscal Year Final Research Report

• Project/Area Number: 20249015
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: MORI Yasuo 京都大学, 大学院・地球環境学堂, 教授 (80212265)
• Project Period (FY): 2008 – 2011
• Keywords: 生体分子医学 / 炎症

Research Abstract

Reactive oxygen species(ROS) induce chemokines responsible for the recruitment of inflammatory cells at inflamed sites in injury or infection. Here, we demonstrate that the plasma membrane Ca^2-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. TRPM2 Ca^2 influx controls the ROS-induced signal cascade responsible for chemokine production which aggravates inflammation. On the other hand, Oxygen(O_2) intake is tightly controlled in order to secure energy production while minimizing the risk of oxidative damage in aerobic organisms. Mammals' respiratory systems have evolved to respond to changes in O_2 availability via the carotid body and other chemoreceptors. Here, our functional examination of the TRP cation channels expressed in mouse vagal chemoreceptors reveals that the TRPA1 channel is activated by O2 and mediates ionic currents in hyperoxia via its prominent sensitivity to cysteine-mediated oxidation. TRPA1 is also activated in hypoxia through relief from O_2-dependent inhibition by prolyl hydroxylases. Hyperoxia-and hypoxia-induced vagal afferent nerve activities and their consequent ventilatory responses are are controlled by TRPA1. Thus, TRPA1 is an O_2 sensor that regulates O_2supply in vivo.

Research Products

• [Journal Article] TRPM2contributes to inflammatory and neuropathicpain through the aggravation of pronociceptive inflammatory responses in mice (2012)
  • Author(s): Haraguchi K, Kawamoto A, Isami K, Maeda S, Kusano A, Asakura K, Shirakawa H, Mori Y, Nakagawa T & Kaneko S.
  • Journal Title: J. Neurosci. Volume: (in press) Pages: 4703-11
  • DOI: DOI:10.1523/JNEUROSCI.4703-11.2012
• [Journal Article] The DC splice-variant of TRPM2 is thehypertonicity-induced cation channel(HICC) in HeLa cells, and the ecto-enzymeCD38 mediates its activation (2011)
  • Author(s): Numata T, Sato K, Christmann J, Marx R, Mori Y, Okada Y & Wehner F.
  • Journal Title: J. Physiol. Volume: (in press) Pages: 220947
  • DOI: DOI:10.1113/jphysiol.2011.220947
• [Journal Article] The juvenile myoclonicepilepsy-related protein EFHC1 interacts with the redox-sensitive TRPM2 channel linked to cell death (2011)
  • Author(s): Katano M, Aguan K, Hara Y, Yamamoto S, Miki T, Sawamura S, Suzuki T, Yamakawa K & Mori Y
  • Journal Title: Cell Calcium Volume: (in press)
  • DOI: DOI:10.1016/j.ceca.2011.12.011
• [Journal Article] Chemical cell-surface receptor engineering using affinity-guided, multivalent organocatalysts (2011)
  • Author(s): Wang H, Koshi Y, Minato D, Nonaka H, Kiyonaka S, Mori Y, Tsukiji S & Hamachi I
  • Journal Title: J. Am. Chem. Soc. Volume: 133 Pages: 12220-1222
  • DOI: DOI:10.1021/ja204422r
• [Journal Article] TRPA1 underlies a sensing mechanism for O_2 (2011)
  • Author(s): Takahashi N, Kuwaki K, Kiyonaka S, Numata T, Kozai D, Mizuno Y, Yamamoto S, Naito S, Knevels E, Carmeliet P, Oga T, Kaneko S, Suga S, Nokami T, Yoshida J & Mori Y
  • Journal Title: Nature Chem. Biol. Volume: 7 Pages: 701-711
  • DOI: DOI:10.1038/NCHEMBIO.640
• [Journal Article] Dendritic cell maturation and chemo taxis is regulated byTRPM2-mediated lysosomal Ca^<2+> release (2011)
  • Author(s): Sumoza-Toledo A, Lange I, Cortado H, Bhagat H, Mori Y, Fleig A, Penner R & Partida-Sanchez S
  • Journal Title: FASEB J. Volume: 25 Pages: 3529-3542
  • DOI: DOI:10.1096/fj.10-178483
• [Journal Article] TRPC3-mediated Ca^<2+> influx contributes toRac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts (2011)
  • Author(s): Kitajima N, Watanabe K, Morimoto S, Sato Y, Kiyonaka S, Hoshijima M, Ikeda Y, Nakaya M, Ide T, Mori Y, Kurose H & Nishida M
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 409 Pages: 108-113
  • DOI: DOI:10.1016/j.bbrc.2011.04.124
• [Journal Article] Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice (2011)
  • Author(s): Uchida K, Dezaki K, Damdindorj B, Inada H, Shiuchi T, Mori Y, Yada T, Minokoshi Y & Tominaga M
  • Journal Title: Diabetes Volume: 60 Pages: 119-126
  • DOI: DOI:10.2337/db10-0276
• [Journal Article] Genetic and pharmacologic inhibition of the Ca^<2+> influx channel TRPC3 protects secretory epithelia from Ca^<2+>-dependent toxicity (2011)
  • Author(s): Kim MS, Lee KP, Yang D, Shin DM, Abramowitz J, Kiyonaka S, Birnbaumer L, Mori Y & Muallem S
  • Journal Title: Gastroenterology Volume: 140 Pages: 2107-2115
  • DOI: DOI:10.1053/j.gastro.2011.02.05
• [Journal Article] The modulation of TRPM7 currents by nafamostat mesilate depends directly uponextracellular concentrations of divalent cations (2010)
  • Author(s): Chen X, Numata T, Li M, Mori Y, Orser BA, Jackson MF, Xiong ZG
  • Journal Title: Mol Brain Volume: 3 Pages: 38
  • DOI: DOI:10.1186/1756-6606-3-38
• [Journal Article] Protein kinase Cχ-specificactivity reporter reveals agonist-evoked nuclear activity controlled by Src family of kinases (2010)
  • Author(s): Kajimoto T, Sawamura S, Tohyama Y, Mori Y & Newton AC
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 41896-41910
  • DOI: DOI:10.1074/jbc.M110.184028
• [Journal Article] Rim2a determines docking and priming states in insulin granule exocytosis (2010)
  • Author(s): Yasuda T, Shibasaki T, Minami K, Takahashi H, Mizoguchi A, Uriu Y, Numata T, Mori Y, Miyazaki JI, Miki T & Seino S
  • Journal Title: Cell Metab. Volume: 12 Pages: 117-129
  • DOI: DOI:10.1016/j.cmet.2010.05.017
• [Journal Article] Inhibition of TRPC6 channel activity contributes to the anti-hypertrophic effects of natriuretic peptides-guanylyl cyclase-Asignaling in the heart (2010)
  • Author(s): Kinoshita H, Kuwahara K, Nishida M, Jiang Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K & Nakao K
  • Journal Title: Circ. Res. Volume: 106 Pages: 1849-1860
  • DOI: DOI:10.1161/CIRCRESAHA.109.208314
• [Journal Article] Differential redox regulation of ORAI channels : a mechanism to tune cellular calcium responses (2010)
  • Author(s): Bogeski I, Kummerow C, Al-Ansary D, Koehler R, Schwarz EC, Kozai D, Takahashi N, Peinelt C, Griesemer D, Bozem B, Mori Y, Hoth M & Niemeyer BA
  • Journal Title: Science Signaling Volume: 3
  • DOI: DOI:10.1126/scisignal.2000672
• [Journal Article] Ca^<2+> influx and protein scaffolding via TRPC3 sustain PKCβand ERK activation in B cells (2010)
  • Author(s): Numaga T, Nishida M, Kiyonaka S, Kato K, Katano K, Mori E, Kurosaki T, Inoue R, Hikida T, Putney Jr JW & Mori M
  • Journal Title: J. Cell Sci. Volume: 123 Pages: 927-938
  • DOI: DOI:10.1242/jcs.061051
• [Journal Article] TRPM1 is a component of the retinal ON bipolar cell transduction channel in themGluR6 cascade (2010)
  • Author(s): Koike C, Obara T, Uriu Y, Numata T, Sanuki R, Miyata K, Koyasu T, Ueno S, Funabiki K, Tani A, Ueda H, Kondo M, Mori Y, Tachibana M & Furukawa T
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 332-337
  • DOI: DOI:10.1073/pnas.0912730107
• [Journal Article] An in vivo fluorescent sensor reveals intracellular Ins(1, 3, 4, 5) P_4 dynamics in single cells (2010)
  • Author(s): Sakaguchi R, Tainaka K, Shimada N, Nakano S, Inoue M, Kiyonaka S, Mori Y & Morii T
  • Journal Title: Angew. Chem. Int. Ed. Volume: 17 Pages: 7381-7386
  • DOI: DOI:10.1002/anie.200903951
• [Journal Article] A single circularly permuted GFP sensor forinositol-1, 3, 4, 5-tetrakisphosphate based on asplit PH domain (2009)
  • Author(s): Sakaguchi R, Endo T, Yamamoto S, Tainaka K, Sugimoto K, Fujieda N, Kiyonaka S, Mori Y & Morii T
  • Journal Title: Bioorg. Med. Chem. Volume: 17 Pages: 7381-7386
  • DOI: DOI:10.1016/j.bmc.2009.08.015
• [Journal Article] A pathogenic C-terminustruncatedPolycistin-2 mutant enhances receptor-activated Ca^<2+> entry via association with TRPC3 and TRPC7 (2009)
  • Author(s): Miyagi K, Kiyonaka S, Yamada K, Miki T, Mori E, Kato K, Numata T, Sawaguchi Y, Numaga T, Kimura T, Kanai Y, Kawano M, Wakamori M, Nomura H, Koni I, Yamagishi M & Mori Y
  • Journal Title: J. Biol. Chem. Volume: 284 Pages: 34400-34412
  • DOI: DOI:10.1074/jbc.M109.015149
• [Journal Article] Molecular characterization of flubendiamide sensitivity in lepidopterousryanodine receptor Ca^<2+> release channel (2009)
  • Author(s): Kato K, Kiyonaka S, Sawaguchi Y, Tohnishi M, Masaki T, Yasokawa N, Mizuno Y, Mori E, Inoue K, Hamachi I, Takeshima H & Mori Y
  • Journal Title: Biochemistry Volume: 48 Pages: 10342-10352
  • DOI: DOI:10.1021/bi900866s
• [Journal Article] Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia (2009)
  • Author(s): Sun H-S, Jackson MF, Martin LJ, Jansen K, Teves L, Cui H, Kiyonaka S, Mori Y, Jones M, Forder JP, Golde TE, Orser BA, MacDonald JF & Tymianski M
  • Journal Title: Nature Neurosci. Volume: 12 Pages: 1300-1307
  • DOI: DOI:10.1038/nn.2395
• [Journal Article] Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via PLC/diacylglycerol and PLA2/￡s-hydroxylase/20-HETE pathways (2009)
  • Author(s): Inoue R, Jensen LJ, Jian Z, Shi J, Hai L, Lurie AI, Henriksen FH, Salmons son M, Morita H, Kawarabayashi Y, Mori M, Mori Y & Ito Y
  • Journal Title: Circ Res. Volume: 104 Pages: 1399-1409
  • DOI: DOI:10.1161/CIRCRESAHA.108.193227
• [Journal Article] STIM protein coupling in the activation of Orai channels (2009)
  • Author(s): Wang Y, Deng X, Zhou Y, Hendron E, Mancarella S, Ritchie MF, Tang XD, Baba Y, Kurosaki T, Mori Y, Soboloff J & Gill DL
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 106 Pages: 7391-7396
  • DOI: DOI:10.1073/pnas.0900293106
• [Journal Article] TRPM2 functions as lysosomal Ca2+ release channel inβ-cells (2009)
  • Author(s): Lange I, Yamamoto Y, Partida-Sanchez S, Mori Y, Fleig A & Penner R
  • Journal Title: Science Signaling Volume: 2, ra23
  • DOI: DOI:10.1126/scisignal.2000278
• [Journal Article] Tetrameric Orai1 is a teardrop-shaped molecule with a long, tapered cytoplasmicdomain (2009)
  • Author(s): Maruyama Y, Ogura T, Mio K, Kato K, Kaneko T, Kiyonaka S, Mori Y & Sato C
  • Journal Title: J. Biol. Chem. Volume: 284 Pages: 13676-13685
  • DOI: DOI:10.1074/jbc.M900812200
• [Journal Article] Selective and direct inhibition of TRPC3channels underlies biological activities of apyrazole compound (2009)
  • Author(s): Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T, Ishii M, Takemoto H, Ojida A, Watanabe K, Uemura A, Kurose H, Morii T, Kobayashi T, Sato Y, Sato C, Hamachi I & Mori Y
  • Journal Title: Proc. Natl. Acad. Volume: 106 Pages: 5400-5405
  • DOI: DOI:10.1073/pnas.0808793106
• [Journal Article] Changes in temperature preferences and energy homeostasis in dystroglycan mutants (2009)
  • Author(s): Takeuchi K, Nakano Y, Kato U, Kaneda M, Aizu M, Awano W, Yonemura S, Kiyonaka S, Mori Y, Yamamoto D & Umeda M
  • Journal Title: Science Volume: 323 Pages: 1740-1743
  • DOI: DOI:10.1126/science.1165712
• [Journal Article] Ca^<2+>-dependent induction of TRPM2 currents in hippocampal neurons (2009)
  • Author(s): Olah ME, Jackson MF, Li H, Perez Y, Sun HS, Kiyonaka S, Mori Y, Tymianski M & Macdonald JF
  • Journal Title: J. Physiol. Volume: 587 Pages: 965-979
  • DOI: DOI:10.1113/jphysiol.2008.162289
• [Journal Article] Molecular characterization of TRPA1 channel activation by cysteine-reactiveinflammatory mediators (2008)
  • Author(s): Takahashi N, Mizuno Y, Kozai D, Yamamoto S, Kiyonaka S, Shibata T, Uchida K & Mori Y
  • Journal Title: Channels Volume: 2 Pages: 287-298
• [Journal Article] Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6 (2008)
  • Author(s): Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A & Inoue R.
  • Journal Title: J. Physiol. Volume: 586 Pages: 4209-4223
  • DOI: DOI:10.1113/jphysiol.2008.156083
• [Journal Article] TRPM2-mediatedCa^<2+> influx induces chemokine production in monocytes that aggravates in flammatoryneutrophil infiltration (2008)
  • Author(s): Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H & Mori Y
  • Journal Title: Nature Med. Volume: 14 Pages: 738-747
  • DOI: DOI:10.1038/nm1758
• [Journal Article] Zinc-Finger Proteins for Site-Specific Protein Positioning on DNA-Origami Structures
  • Author(s): Nakata E, Liew F, Uwatoko C, Kiyonaka S, Mori Y, Katsuda Y, Endo M, Sugiyama H & Morii T.
  • Journal Title: Angew. Chem. Int. Ed. Volume: (in press)
• [Journal Article] Dependence of NMDA/GSK-3βmediatedmetaplasticity on TRPM2 channels at hippocampal CA3-CA1 synapses
  • Author(s): Xie YF, Belrose JC, Lei G, Tymianski T, Mori Y, MacDonald JF & Michael F, Jackson MF
  • Journal Title: Mol. Brain Volume: (in press)
• [Presentation] Redox physiology of TRP channels. (2011)
  • Author(s): 森泰生
  • Organizer: The 1^<st> international meeting on ion channel signaling mechanisms from basic science to clinical application
  • Place of Presentation: モロッコ(マラケシュ)
  • Year and Date: 2011-11-03
• [Presentation] Molecular characterization of benzenedicarboxamide agonist sensitivity in lepidopterous ryanodine receptor Ca^<2+> release channel. (2010)
  • Author(s): 森泰生
  • Organizer: The 12th IUPAC international congress of pesticide chemistry
  • Place of Presentation: オーストラリア(メルボルン)
  • Year and Date: 2010-07-07
• [Presentation] Activation and physiological properties of TRP channels (2009)
  • Author(s): 森泰生
  • Organizer: 2009 international union of physiological sciences(IUPS): international conference of physiological sciences
  • Place of Presentation: 韓国(釜山)
  • Year and Date: 2009-01-15
• [Presentation] Integration of calcium signals by TRP channel some (2008)
  • Author(s): 森泰生
  • Organizer: FASEB summer research conferences : calcium and cell function
  • Place of Presentation: アメリカ合衆国(コロラド)
  • Year and Date: 2008-06-08
• [Presentation] ROS-and RNS-sensor TRP channels : activation mechanism and physiological function (2008)
  • Author(s): 森泰生
  • Organizer: Centennial anniversary & the 32^<nd> congress of Korean medical association
  • Place of Presentation: 韓国(ソウル)
  • Year and Date: 2008-05-02
• [Book] TRPチャネル日本薬理学雑誌 (2012)
  • Author(s): 高田宜則、森泰生
  • Total Pages: 39-406
• [Book] ファルマシア (2012)
  • Author(s): 清中茂樹、高橋重成、森泰生
  • Total Pages: 31-36
• [Book] 細胞工学 (2012)
  • Author(s): 森泰生
• [Book] 新着論文レビュー (2011)
  • Author(s): 高橋重成、森泰生
  • URL: http://first.lifesciencedb.jp/archives/
• [Book] トランスポートソームの世界 (2011)
  • Author(s): 森泰生、清中茂樹
  • Total Pages: 291-296
• [Book] トランスポートソームの世界 (2011)
  • Author(s): 森泰生、沼田朋大, 高橋重成
  • Total Pages: 73-77
• [Book] イオンチャネルトランスポートソームの世界 (2011)
  • Author(s): 森泰生、高橋重成
  • Total Pages: 11-15
• [Book] BRAIN and NERVE (2011)
  • Author(s): 中尾章人、高田宜則、森泰生
  • Total Pages: 657-667
• [Book] 遺伝子医学MOOK (2011)
  • Author(s): 瓜生幸嗣、清中茂樹、高田宜則、森泰生
  • Total Pages: 210-219
• [Book] 日本農薬学会誌 (2011)
  • Author(s): 清中茂樹、加藤賢太、森泰生
  • Total Pages: 102-105
• [Book] G. I. Research (2011)
  • Author(s): 香西大輔、輪島輝明、清水俊一、森泰生
  • Total Pages: 4-12
• [Book] Frontiers Pharmacol (2011)
  • Author(s): Takahashi N & Mori Y
  • Total Pages: 58
• [Book] Channels (2011)
  • Author(s): Mori Y, Kiyonaka S & Kanai Y
  • Total Pages: 387-390
• [Book] Cell Calcium (2011)
  • Author(s): Takahashi N, Kozai D, Kobayashi R, Ebert M & Mori Y
  • Total Pages: 279-290
• [Book] Advances in Experimental Medicine and Biology : Transient Receptor Potential Channels (2011)
  • Author(s): Mori Y, Kajimoto T, Nakao A, Takahashi N, & Kiyonaka S
  • Total Pages: 373-89
  • Publisher: Springer
• [Book] Activation of TRP channels in mammalian systems. In"Handbook of Experimental Pharmacology : TRP channels in health and disease" (2011)
  • Author(s): Numata T, Kiyonaka S, Kato K, Takahashi N & Mori Y
  • Total Pages: 43-90
  • Publisher: CRC press
• [Book] 鼻アレルギーフロンティア (2010)
  • Author(s): 加藤賢太、梶本武利、森泰生
  • Total Pages: 34-40
• [Book] ファルマシア (2010)
  • Author(s): 清中茂樹、加藤賢太、西田基宏、森泰生
  • Total Pages: 303-311
• [Book] TRPM1 : a vertebrate TRP channel responsible for retinal ON bipolar function. Cell Calcium (2010)
  • Author(s): Koike C, Numata T, Ueda H, Mori Y & Furukawa T
  • Total Pages: 95-101
• [Book] Chemical Physiology of Oxidative Stress-Activated TRPM2 and TRPC5 Channel. Prog. Biophys. Mol. Biol. (2010)
  • Author(s): Yamamoto S, Takahashi N & Mori Y
  • Total Pages: 18-27
• [Book] 化学 (2009)
  • Author(s): 沼田朋大、香西大輔、高橋重成、加藤賢太、瓜生幸嗣、山本伸一郎、金子雄、眞本達生、森泰生、清中茂樹、高橋重成
  • Total Pages: 27-33
• [Book] 化学 (2009)
  • Author(s): 森泰生
  • Total Pages: 12-14
• [Book] 日本薬理学雑誌 (2009)
  • Author(s): 山本伸一郎、清水俊一、森泰生
  • Total Pages: 122-126
• [Book] 実験医学 (2009)
  • Author(s): 高橋重成、山本伸一郎、森泰生
  • Total Pages: 2494-2502
• [Book] 蛋白質核酸酵素 (2009)
  • Author(s): 山本伸一郎、高橋重成、清中茂樹、森泰生
  • Total Pages: 212-223
• [Book] CXCL-2臨床免疫・アレルギー科 (2008)
  • Author(s): 梶本武利、小林良平、森泰生
  • Total Pages: 658-661
• [Book] 生化学 (2008)
  • Author(s): 清中茂樹、三木崇史、瓜生幸嗣、森泰生
  • Total Pages: 80