Thrombin aggravates hypoxia/reoxygenation injury of astrocytes by activating the autophagy pathway mediated by SPRED2

凝血酶通过激活SPRED2介导的自噬途径加重星形胶质细胞缺氧/复氧损伤

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作者:Xiaoning Wang, Weiwei Lu, Bing Liu, Yunhe Xu

Abstract

Autophagy plays an important role in ischemia/reperfusion brain injury, however, the signaling pathways involved in cell autophagy are not fully understood. The present study aimed to investigate the roles and molecular mechanisms of thrombin and Sprouty-related EVH1 domain-2 (SPRED2) on autophagy in hypoxia/reoxygenation (H/R) induced astrocytes. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of thrombin and SPRED2. Western blot analysis was also performed to detect the protein expression levels of Beclin 1, microtubule-associated protein light chain 3 (LC3)-II and LC3-I. The MTT assay was performed to assess cell viability, while ELISA was performed to determine the supernatant levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. The results demonstrated that the effects of H/R induction on inflammatory factor secretion, oxidative stress, autophagy and cell viability in astrocytes were aggravated by thrombin, the effects of which were reversed following SPRED2 knockdown. Taken together, the results of the present study suggest that thrombin aggravates H/R injury in astrocytes by activating the SPRED2-mediated autophagy.

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