TRPA1 underlies a sensing mechanism for O 2

Nobuaki Takahashi, Tomoyuki Kuwaki, Shigeki Kiyonaka, Tomohiro Numata, Daisuke Kozai, Yusuke Mizuno, Shinichiro Yamamoto, Shinji Naito, Ellen Knevels, Peter Carmeliet, Toru Oga, Shuji Kaneko, Seiji Suga, Toshiki Nokami, Jun Ichi Yoshida, Yasuo Mori

Research output: Contribution to journalArticle

157 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)701-711
Number of pages11
JournalNature Chemical Biology
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Fingerprint

Hyperoxia
Prolyl Hydroxylases
Cell Respiration
Transient Receptor Potential Channels
Sensory Receptor Cells
Disulfides
Oxidation-Reduction
Cysteine
Oxygen
Genes
Hypoxia

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Takahashi, N., Kuwaki, T., Kiyonaka, S., Numata, T., Kozai, D., Mizuno, Y., ... Mori, Y. (2011). TRPA1 underlies a sensing mechanism for O 2 . Nature Chemical Biology, 7(10), 701-711. https://doi.org/10.1038/nchembio.640

TRPA1 underlies a sensing mechanism for O 2 . / 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.

In: Nature Chemical Biology, Vol. 7, No. 10, 10.2011, p. 701-711.

Research output: Contribution to journalArticle

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 2011, 'TRPA1 underlies a sensing mechanism for O 2 ', Nature Chemical Biology, vol. 7, no. 10, pp. 701-711. https://doi.org/10.1038/nchembio.640
Takahashi N, Kuwaki T, Kiyonaka S, Numata T, Kozai D, Mizuno Y et al. TRPA1 underlies a sensing mechanism for O 2 . Nature Chemical Biology. 2011 Oct;7(10):701-711. https://doi.org/10.1038/nchembio.640
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. / TRPA1 underlies a sensing mechanism for O 2 . In: Nature Chemical Biology. 2011 ; Vol. 7, No. 10. pp. 701-711.
@article{3dcdd8a2128449d7a277d606c5098f8d,
title = "TRPA1 underlies a sensing mechanism for O 2",
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.",
author = "Nobuaki Takahashi and Tomoyuki Kuwaki and Shigeki Kiyonaka and Tomohiro Numata and Daisuke Kozai and Yusuke Mizuno and Shinichiro Yamamoto and Shinji Naito and Ellen Knevels and Peter Carmeliet and Toru Oga and Shuji Kaneko and Seiji Suga and Toshiki Nokami and Yoshida, {Jun Ichi} and Yasuo Mori",
year = "2011",
month = "10",
doi = "10.1038/nchembio.640",
language = "English",
volume = "7",
pages = "701--711",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - TRPA1 underlies a sensing mechanism for O 2

AU - Takahashi, Nobuaki

AU - Kuwaki, Tomoyuki

AU - Kiyonaka, Shigeki

AU - Numata, Tomohiro

AU - Kozai, Daisuke

AU - Mizuno, Yusuke

AU - Yamamoto, Shinichiro

AU - Naito, Shinji

AU - Knevels, Ellen

AU - Carmeliet, Peter

AU - Oga, Toru

AU - Kaneko, Shuji

AU - Suga, Seiji

AU - Nokami, Toshiki

AU - Yoshida, Jun Ichi

AU - Mori, Yasuo

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052960971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052960971&partnerID=8YFLogxK

U2 - 10.1038/nchembio.640

DO - 10.1038/nchembio.640

M3 - Article

C2 - 21873995

AN - SCOPUS:80052960971

VL - 7

SP - 701

EP - 711

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 10

ER -