Blocking transient receptor potential vanilloid 2 channel in astrocytes enhances astrocyte‐mediated neuroprotection after oxygen–glucose deprivation and reoxygenation. (19th August 2016)

• Record Type: Journal Article
• Authors: Zhang, Han; Xiao, Jun; Hu, Zheng; Xie, Minjie; Wang, Wei; He, Dan
• Editors: Kirik, Deniz
• Is Part Of: European journal of neuroscience. Volume 44:Number 7(2016:Oct.)
• Page Start: 2493
• Page End: 2503
• Publication Date: 2016-08-19
• Subjects: intracellular Ca2+ -- ischemic stroke -- nerve growth factor -- proliferation; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13352
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: 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 (TRPV2), 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 TRPV2 is functional because Ca 2+ imaging showed that activating the TRPV2 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 TRPV2, it promoted the proliferation of astrocytes. Additionally, blocking the TRPV2 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 TRPV2 caused the phosphorylation of JNK. These indicated that blocking the TRPV2 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 TRPV2 channel in astrocytes might be a potential new therapeutic strategy in ischemic stroke. Abstract : Transient receptor potential vanilloid 2 (TRPV2) channel expresses functionally in rat cortical astrocytes and oxygen‐glucose deprivation and reoxygenation treatment enhances the expression. Blocking the TRPV2 channel in astrocytes promotes cell proliferation and the secretion of nerve growth factor via the mitogen‐activated protein kinase‐c‐JunN‐terminalkinase pathway. TRPV2 channel may be a candidate target for the astrocyte‐mediated therapy in ischemic stroke.