Physiologicalsignificance or redox-sensitive ion channels
| Project/Area Number |
23800035
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | TRPチャネル / 酸素 / 低酸素 / 高酸素 / レドックス / 呼吸 / TRPA1 / 迷走神経 / イオンチャネル |
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| 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.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] TRPA1 underlies a sensing mechanism for O_22011
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
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Journal Title
Nature Chem. Biol.
Volume: 7
Issue: 10
Pages: 701-711
DOI
Related Report
Peer Reviewed
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[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
Related Report
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[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
Related Report
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[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
Related Report
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