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Title: Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS
Authors: Miyake, Takahito  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4356-5883 (unconfirmed)
Nakamura, Saki
Zhao, Meng
So, Kanako
Inoue, Keisuke
Numata, Tomohiro
Takahashi, Nobuaki  kyouindb  KAKEN_id
Shirakawa, Hisashi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4129-0978 (unconfirmed)
Mori, Yasuo  kyouindb  KAKEN_id
Nakagawa, Takayuki  kyouindb  KAKEN_id
Kaneko, Shuji  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-5152-5809 (unconfirmed)
Author's alias: 三宅, 崇仁
中川, 貴之
金子, 周司
Issue Date: 15-Sep-2016
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 7
Thesis number: 12840
Abstract: Mammalian transient receptor potential ankyrin 1 (TRPA1) is a polymodal nociceptor that plays an important role in pain generation, but its role as a cold nociceptor is still controversial. Here, we propose that TRPA1 can sense noxious cold via transduction of reactive oxygen species (ROS) signalling. We show that inhibiting hydroxylation of a proline residue within the N-terminal ankyrin repeat of human TRPA1 by mutation or using a prolyl hydroxylase (PHD) inhibitor potentiates the cold sensitivity of TRPA1 in the presence of hydrogen peroxide. Inhibiting PHD in mice triggers mouse TRPA1 sensitization sufficiently to sense cold-evoked ROS, which causes cold hypersensitivity. Furthermore, this phenomenon underlies the acute cold hypersensitivity induced by the chemotherapeutic agent oxaliplatin or its metabolite oxalate. Thus, our findings provide evidence that blocking prolyl hydroxylation reveals TRPA1 sensitization to ROS, which enables TRPA1 to convert ROS signalling into cold sensitivity.
Description: 人はなぜ「冷たい」を「痛い」と感じるのか ―活性酸素と痛みセンサーTRPA1がカギを握る―. 京都大学プレスリリース. 2016-09-16.
Rights: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/216607
DOI(Published Version): 10.1038/ncomms12840
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2016/160915_1.html
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