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Title: | TRPA1 underlies a sensing mechanism for O(2). |
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 https://orcid.org/0000-0001-5152-5809 (unconfirmed) Suga, Seiji Nokami, Toshiki Yoshida, Jun-Ichi Mori, Yasuo |
Issue Date: | 28-Aug-2011 |
Publisher: | Nature Publishing Group |
Citation: | 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 JI, Mori Y. TRPA1 underlies a sensing mechanism for O(2). Nat Chem Biol. 2011 Aug 28. doi: 10.1038/nchembio.640. [Epub ahead of print] PubMed PMID: 21873995 |
Journal title: | Nature chemical biology |
Volume: | 7 |
Issue: | 10 |
Start page: | 701 |
End page: | 711 |
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. |
Description: | 新たな生体内酸素センサー機構の発見. 京都大学プレスリリース. 2011-08-29. |
Rights: | © 2011 Nature America, Inc. All rights reserved. 許諾条件により本文は2012-02-28に公開. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/145668 |
DOI(Published Version): | 10.1038/nchembio.640 |
PubMed ID: | 21873995 |
Related Link: | https://www.kyoto-u.ac.jp/static/ja/news_data/h/h1/news6/2011/110829_1.htm http://www.nature.com/nchembio/journal/vaop/ncurrent/pdf/nchembio.640.pdf |
Appears in Collections: | Journal Articles |
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