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Blocking transient receptor potential vanilloid 2 channel in astrocytes enhances astrocyte‐mediated neuroprotection after oxygen–glucose deprivation and reoxygenation
Author(s) -
Zhang Han,
Xiao Jun,
Hu Zheng,
Xie Minjie,
Wang Wei,
He Dan
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13352
Subject(s) - trpv , neuroprotection , transient receptor potential channel , astrocyte , chemistry , microbiology and biotechnology , endocrinology , medicine , pharmacology , receptor , trpv1 , biology , biochemistry , central nervous system
Astrocytes play important roles in homeostatic regulation in the central nervous system and are reported to influence the outcome of ischemic injury. Regulating Ca 2+ signaling of astrocytes is a promising strategy for stroke therapy. Herein, we report for the first time that transient receptor potential vanilloid 2 ( TRPV 2), a Ca 2+ ‐permeable channel that is important in osmotic balance regulation, expresses in rat cortical astrocytes by immunofluorescence. Moreover, oxygen‐glucose deprivation and reoxygenation ( OGD /R) treatment enhanced the expression. The TRPV 2 is functional because Ca 2+ imaging showed that activating the TRPV 2 channel in cultured astrocytes increased intracellular Ca 2+ level and the increment of intracellular Ca 2+ level expanded when astrocytes were treated with OGD /R. Staining with 5‐ethynyl‐2′‐deoxyuridine (EdU) revealed that while blocking the TRPV 2, it promoted the proliferation of astrocytes. Additionally, blocking the TRPV 2 in astrocytes increased the synthesis of nerve growth factor ( NGF ) mRNA and the secretion of NGF by real‐time PCR and enzyme‐linked immunosorbent assay respectively. We further found that the increased secretion of NGF could be reversed by c‐JunN‐terminalkinase ( JNK ) inhibitor and blocking the TRPV 2 caused the phosphorylation of JNK . These indicated that blocking the TRPV 2 induced NGF secretion via the mitogen‐activated protein kinase ( MAPK )‐ JNK signaling pathway. As the promoted proliferation of astrocytes and secretion of NGF were reported to have neuroprotective effects in the early stage of stroke, we concluded that targeting the TRPV 2 channel in astrocytes might be a potential new therapeutic strategy in ischemic stroke.