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- Title
TRPA1 underlies a sensing mechanism for O<sub>2</sub>.
- Authors
Takahashi, Nobuaki; Kuwaki, Tomoyuki; Kiyonaka, Shigeki; Numata, Tomohiro; Kozai, Daisuke; Mizuno, Yusuke; Yamamoto, Shinichiro; Naito, Shinji; Knevels, Ellen; Carmeliet, Peter; Oga, Toru; Kaneko, Shuji; Suga, Seiji; Nokami, Toshiki; Yoshida, Jun-ichi; Mori, Yasuo
- Abstract
Oxygen (O2) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O2, it is critical to elucidate the molecular mechanisms responsible for O2 sensing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with different redox potentials reveals the capability of TRPA1 to sense O2. O2 sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O2-dependent inhibition on TRPA1 activity in normoxia, direct O2 action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O2-sensing mechanism mediated by TRPA1.
- Subjects
ACTIVE oxygen in the body; CELL respiration; TRP channels; PROLINE hydroxylase; HYPEROXIA; HYPOXEMIA
- Publication
Nature Chemical Biology, 2011, Vol 7, Issue 10, p701
- ISSN
1552-4450
- Publication type
Article
- DOI
10.1038/nchembio.640