| 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
|
| Project Status |
Completed (Fiscal Year 2012)
|
| 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 |
|---|
| 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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