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Title: | Identification of a prostaglandin D 2 metabolite as a neuritogenesis enhancer targeting the TRPV1 ion channel |
Authors: | Shibata, Takahiro Takahashi, Katsuhiro Matsubara, Yui Inuzuka, Emi Nakashima, Fumie Takahashi, Nobuaki Kozai, Daisuke Mori, Yasuo Uchida, Koji |
Author's alias: | 高橋, 重成 香西, 大輔 森, 泰生 |
Issue Date: | 16-Feb-2016 |
Publisher: | Nature Publishing Group |
Journal title: | Scientific Reports |
Volume: | 6 |
Thesis number: | 21261 |
Abstract: | Mast cells play important roles in allergic inflammation by secreting various mediators. In the present study, based on the finding that the medium conditioned by activated RBL-2H3 mast cells enhanced the nerve growth factor (NGF)-induced neuritogenesis of PC12 cells, we attempted to isolate an active compound from the mast cell conditioned culture medium. Our experiment identified 15-deoxy-δ " 12, 14-PGJ2 (15d-PGJ2), one of the PGD 2 metabolites, as a potential enhancer of neuritogenesis. 15d-PGJ2 strongly enhanced the neuritogenesis elicited by a low-concentration of NGF that alone was insufficient to induce the neuronal differentiation. This 15d-PGJ2 effect was exerted in a Ca 2+-dependent manner, but independently of the NGF receptor TrkA. Importantly, 15d-PGJ2 activated the transient receptor potential vanilloid-type 1 (TRPV1), a non-selective cation channel, leading to the Ca 2+ influx. In addition, we observed that (i) NGF promoted the insertion of TRPV1 into the cell surface membrane and (ii) 15d-PGJ2 covalently bound to TRPV1. These findings suggest that the NGF/15d-PGJ2-induced neuritogenesis may be regulated by two sets of mechanisms, one for the translocation of TRPV1 into the cell surface by NGF and one for the activation of TRPV1 by 15d-PGJ2. Thus, there is most likely a link between allergic inflammation and activation of the neuronal differentiation. |
Rights: | 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/2433/216086 |
DOI(Published Version): | 10.1038/srep21261 |
PubMed ID: | 26879669 |
Appears in Collections: | Journal Articles |
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