LncRNA-MEG3 attenuates hyperglycemia-induced damage by enhancing mitochondrial translocation of HSP90A in the primary hippocampal neurons

作者：Wanqing Zhou, Zhihua Wang, Yuanyuan Tao, Cheng Chen, Qian Zhang, Zhuoyi Liu, Longyan Li, Pingping Xia, Zhi Ye · 发表于：Experimental Cell Research · 年份：2022 · DOI：10.1016/j.yexcr.2022.113320 · 被引用次数：7 · 研究领域：Cancer-related molecular mechanisms research、Mitochondrial Function and Pathology、Sirtuins and Resveratrol in Medicine

The diabetic cognitive impairments are associated with high-glucose (HG)-induced mitochondrial dysfunctions in the brain. Our previous studies demonstrated that long non-coding RNA (lncRNA)-MEG3 alleviates diabetic cognitive impairments. However, the underlying mechanism has still remained elusive. Therefore, this study was designed to investigate whether the mitochondrial translocation of HSP90A and its phosphorylation are involved in lncRNA-MEG3-mediated neuroprotective effects of mitochondrial functions in HG-treated primary hippocampal neurons and diabetic rats. The primary hippocampal neurons were exposed to 75 mM glucose for 72 h to establish a HG model in vitro. Firstly, the RNA pull-down and RNA immunoprecipitation (RIP) assays clearly indicated that lncRNA-MEG3-associated mitochondrial proteins were Annexin A2, HSP90A, and Plectin. Although HG promoted the mitochondrial translocation of HSP90A and Annexin A2, lncRNA-MEG3 over-expression only enhanced the mitochondrial translocation of HSP90A, rather than Annexin A2, in the primary hippocampal neurons treated with or without HG. Meanwhile, Plectin mediated the mitochondrial localization of lncRNA-MEG3 and HSP90A. Furthermore, HSP90A threonine phosphorylation participated in regulating mitochondrial translocation of HSP90A, and lncRNA-MEG3 also enhanced mitochondrial translocation of HSP90A through suppressing HSP90A threonine phosphorylation. Finally, the anti-apoptotic role of mitochondrial translocation of HSP90A wa...