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Title: Sphingosine-1-phosphate induces Ca²⁺ signaling and CXCL1 release via TRPC6 channel in astrocytes.
Authors: Shirakawa, Hisashi  kyouindb  KAKEN_id  orcid (unconfirmed)
Katsumoto, Rumi
Iida, Shota
Miyake, Takahito  kyouindb  KAKEN_id  orcid (unconfirmed)
Higuchi, Takuya
Nagashima, Takuya
Nagayasu, Kazuki  kyouindb  KAKEN_id
Nakagawa, Takayuki  kyouindb  KAKEN_id  orcid (unconfirmed)
Kaneko, Shuji  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 白川, 久志
長島, 卓也
永安, 一樹
中川, 貴之
金子, 周司
Keywords: astrocytes
calcium signaling
sphingosine 1‐phosphate
TRP channels
Issue Date: Jun-2017
Publisher: Wiley
Journal title: Glia
Volume: 65
Issue: 6
Start page: 1005
End page: 1016
Abstract: A biologically active lipid, sphingosine‐1‐phosphate (S1P) is highly abundant in blood, and plays an important role in regulating the growth, survival, and migration of many cells. Binding of the endogenous ligand S1P results in activation of various signaling pathways via G protein‐coupled receptors, some of which generates Ca²⁺ mobilization. In astrocytes, S1P is reported to evoke Ca²⁺ signaling, proliferation, and migration; however, the precise mechanisms underlying such responses in astrocytes remain to be elucidated. Transient receptor potential canonical (TRPC) channels are Ca²⁺‐permeable cation channels expressed in astrocytes and involved in Ca²⁺ influx after receptor stimulation. In this study, we investigated the involvement of TRPC channels in S1P‐induced cellular responses. In Ca²⁺ imaging experiments, S1P at 1 μM elicited a transient increase in intracellular Ca²⁺ in astrocytes, followed by sustained elevation. The sustained Ca²⁺ response was markedly suppressed by S1P₂ receptor antagonist JTE013, S1P₃ receptor antagonist CAY10444, or non‐selective TRPC channel inhibitor Pyr2. Additionally, S1P increased chemokine CXCL1 mRNA expression and release, which were suppressed by TRPC inhibitor, inhibition of Ca²⁺ mobilization, MAPK pathway inhibitors, or knockdown of the TRPC channel isoform TRPC6. Taken together, these results demonstrate that S1P induces Ca²⁺ signaling in astrocytes via Gq‐coupled receptors S1P₂ and S1P₃, followed by Ca²⁺ influx through TRPC6 that could activate MAPK signaling, which leads to increased secretion of the proinflammatory or neuroprotective chemokine CXCL1.
Rights: This is the peer reviewed version of the following article: Shirakawa, H, Katsumoto, R, Iida, S, et al. Sphingosine‐1‐phosphate induces Ca²⁺ signaling and CXCL1 release via TRPC6 channel in astrocytes. Glia. 2017; 65: 1005– 1016., which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
The full-text file will be made open to the public on 18 April 2018 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1002/glia.23141
PubMed ID: 28300348
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