Orexin-A promotes Glu uptake by OX1R/PKCα/ERK1/2/GLT-1 pathway in astrocytes and protects co-cultured astrocytes and neurons against apoptosis in anoxia/hypoglycemic injury in vitro

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• 作者：Qing Shu ; Jianhuai Zhang ; Wei Ma ; Youying Lei…
• 关键词：Orexin ; A ; Ischemic stroke ; Neurons ; GLT ; 1 ; PKCα–ERK1/2 pathway
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：425
• 期：1-2
• 页码：103-112
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Medical Biochemistry; Oncology; Cardiology;
• 出版者：Springer US
• ISSN：1573-4919
• 卷排序：425

文摘

Orexin-A, which is an endogenous neuropeptide, is reported to have a protective role in ischemic stroke. High-concentration glutamic acid (Glu) induced by hypoxia injury in ischemic stroke can be inhibited by glial glutamate transporter GLT-1 which is only expressed in astroglia cells. A previous study reported that Orexin-A may regulate GLT-1 expression. However, the role of orexin-A in the regulation of GLT-1 in ischemic stroke still remains unclear. In this study, we aimed to investigate the effect and the underlying mechanism of orexin-A on Glu uptake in astrocytes in vitro and this effect on protecting the neurons from anoxia/hypoglycemic injury. The expression of GLT-1 significantly increased in the astrocytes with orexin-A treatment under anoxia/hypoglycemic conditions, promoting the uptake of Glu and inhibiting the apoptosis of co-cultured cells of astrocytes and neurons. However, these effects were significantly weakened by treatment with orexin-A receptor 1 (OX1R) antagonist. Orexin-A significantly up-regulated the expressions of PKCα and ERK1/2 under anoxia/hypoglycemic conditions in astrocytes, whereas the OX1R antagonist markedly reversed the effect. Furthermore, PKCα or ERK1/2 inhibitor significantly constrained the GLT-1 expression in astrocytes and facilitated the apoptosis of co-cultured cells, and GLT-1 overexpression could reverse those effects of PKCα or ERK1/2 inhibitor. Taken together, orexin-A promoted the GLT-1 expression via OX1R/PKCα/ERK1/2 pathway in astrocytes and protected co-cultured cells against anoxia/hypoglycemic injury.