Physiologicalsignificance or redox-sensitive ion channels

2012 Fiscal Year Final Research Report

• Project/Area Number: 23800035
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyoto University
• Principal Investigator: TAKAHASHI Nobuaki 京都大学, 先端医工学研究ユニット, 助教 (70604635)
• Project Period (FY): 2011 – 2012
• Keywords: TRPチャネル / 酸素

Research Abstract

Oxygen (O_2) intake is tightly controlled to minimize the risk of oxidative damage while securing energy production in aerobic organisms. The O_2sensors for respiratory mechanisms to protect against O_2 toxicity, however, are still elusive. Our systematic evaluation of redox sensitivity of TRP cation channels reveals that the TRPA1 channel senses O_2availability. Hyperoxia sensing is based upon disparate mechanisms: while prolyl hydroxylases (PHDs) exert O_2-dependent inhibition on TRPA1 activity in normoxia, direct O_2 action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Interestingly, in hypoxia, TRPA1 is activated through relief from the same PHD-mediated inhibition. In Trpa1-deficient mice, ventilatory responses to hyperoxia and hypoxia are severely impaired. As a consequence of their defects, pulmonary inflammation and hypertension are abnormally induced in normoxia, and are aggravated in hyperoxia and hypoxia, respectively. Thus, TRPA1 is an O_2sensor that regulates O_2supplyin vivo.

Research Products

• [Journal Article] TRP channels: sensors and transducers of gasotransmitter signals (2012)
  • Author(s): Takahashi N, Kozai D, Mori Y
  • Journal Title: Front Physiol Volume: 3 Pages: 324
  • Peer Reviewed
• [Journal Article] TRP Channels as Sensors and Signal Integrators of Redox Status Changes (2011)
  • Author(s): Takahashi N, Mori Y
  • Journal Title: Front Pharmacol Volume: 2 Pages: 58
  • DOI: doi:10.3389/fphar.2011.00058
  • Peer Reviewed
• [Journal Article] TRPA1 underlies a sensing mechanism for O_2 (2011)
  • Author(s): Takahashi N, Kuwaki T, 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: 2 Pages: 701-711
  • DOI: doi:10.1038/nchembio.640
  • Peer Reviewed
• [Journal Article] TRP channels as sensors of oxygen availability
  • Author(s): Numata T, Ogawa N, Takahashi N, Mori Y
  • Journal Title: Pflugers Arch
  • URL: http://link.springer.com/article/10.1007%2Fs00424-013-1237-9
  • Peer Reviewed
• [Presentation] Nitric-oxide directly activates TRP channels via oxidative cysteine modification (2013)
  • Author(s): Nobuaki Takahashi, Yasuo Mori
  • Organizer: Biophysical Society 57th Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2013-02-04
• [Presentation] TRPC5チャネル複合体によるCa^2+ 動員およびNO産生の制御 (2012)
  • Author(s): 高橋重成, 吉田卓史, 山本伸一郎, 眞本達生, 飯沼ゆり子, 原雄二, 森泰生
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-12-15
• [Presentation] TRPチャネルによる新たな生体内酸素感受機構 (2012)
  • Author(s): 高橋重成
  • Organizer: 岐阜薬科大学 大学院薬学研究科特別講義
  • Place of Presentation: 岐阜市
  • Year and Date: 2012-05-28
• [Presentation] Sensing of O_2 availability by TRPA1 regulates O_2 intake (2012)
  • Author(s): Nobuaki Takahashi, Tomoyuki Kuwaki, Shigeki Kiyonaka, Tomohiro Numata, Yasuo Mori
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本市
  • Year and Date: 2012-03-30
• [Presentation] TRPA1 は体内への酸素供給を制御する酸素センサーである (2011)
  • Author(s): 高橋重成, 森泰生
  • Organizer: 第18回MPO研究会
  • Place of Presentation: 熊本市
  • Year and Date: 2011-10-28
• [Book] 血管医学 (2012)
  • Author(s): 植田誉志史, 高橋重成, 森泰生
  • Total Pages: 13
  • Publisher: 新たな酸素センサー/チャネルによる低酸素応答制御
• [Book] 実験医学 (2012)
  • Author(s): 植田誉志史, 高橋重成, 森泰生
  • Total Pages: 30
  • Publisher: TRPA1チャネルを介した酸素・活性酸素種センシング
• [Book] 実験医学 (2012)
  • Author(s): 高橋重成, 植田誉志史, 森泰生
  • Total Pages: 30
  • Publisher: TRP チャネルを介する新しい酸素センシング機構
• [Book] 医学のあゆみ (2012)
  • Author(s): 高橋重成
  • Total Pages: 241
  • Publisher: TRPA1チャネルによる酸素感受性
• [Remarks]
  • URL: http://www.sbchem.kyoto-u.ac.jp/mori-lab/