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Sphingosine‐1‐phosphate induces C a 2+ signaling and CXCL 1 release via TRPC 6 channel in astrocytes
Author(s) -
Shirakawa Hisashi,
Katsumoto Rumi,
Iida Shota,
Miyake Takahito,
Higuchi Takuya,
Nagashima Takuya,
Nagayasu Kazuki,
Nakagawa Takayuki,
Kaneko Shuji
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23141
Subject(s) - trpc , trpc6 , microbiology and biotechnology , transient receptor potential channel , biology , sphingosine 1 phosphate , signal transduction , sphingosine , receptor , biochemistry
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 Ca 2+ mobilization. In astrocytes, S1P is reported to evoke Ca 2+ signaling, proliferation, and migration; however, the precise mechanisms underlying such responses in astrocytes remain to be elucidated. Transient receptor potential canonical (TRPC) channels are Ca 2+ ‐permeable cation channels expressed in astrocytes and involved in Ca 2+ influx after receptor stimulation. In this study, we investigated the involvement of TRPC channels in S1P‐induced cellular responses. In Ca 2+ imaging experiments, S1P at 1 μM elicited a transient increase in intracellular Ca 2+ in astrocytes, followed by sustained elevation. The sustained Ca 2+ response was markedly suppressed by S1P 2 receptor antagonist JTE013, S1P 3 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 Ca 2+ mobilization, MAPK pathway inhibitors, or knockdown of the TRPC channel isoform TRPC6. Taken together, these results demonstrate that S1P induces Ca 2+ signaling in astrocytes via G q ‐coupled receptors S1P 2 and S1P 3 , followed by Ca 2+ influx through TRPC6 that could activate MAPK signaling, which leads to increased secretion of the proinflammatory or neuroprotective chemokine CXCL1.