Title: TRPA1 underlies a sensing mechanism for O2
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 #
Issue Date: Oct-2011
Publisher: Nature Pub. Group
Series Title: Nature Chemical Biology vol:7 issue:10 pages:701-711
Article number: 10.1038/nchembio.640
Abstract: Oxygen (O(2)) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O(2), it is critical to elucidate the molecular mechanisms responsible for O(2) 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 O(2). O(2) sensing is based upon disparate processes: whereas 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. 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 O(2)-sensing mechanism mediated by TRPA1.
ISSN: 1552-4450
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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