PMID- 35998683 OWN - NLM STAT- MEDLINE DCOM- 20220913 LR - 20221005 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 419 IP - 2 DP - 2022 Oct 15 TI - LncRNA-MEG3 attenuates hyperglycemia-induced damage by enhancing mitochondrial translocation of HSP90A in the primary hippocampal neurons. PG - 113320 LID - S0014-4827(22)00313-5 [pii] LID - 10.1016/j.yexcr.2022.113320 [doi] AB - 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 was found to be associated with inhibiting death receptor 5 (DR5) in HG-treated primary hippocampal neurons and diabetic rats. Taken together, lncRNA-MEG3 could improve mitochondrial functions in HG-exposed primary hippocampal neurons, and the underlying mechanisms were involved in enhanced mitochondrial translocation of HSP90A via suppressing HSP90A threonine phosphorylation, which may reveal a potential therapeutic target for diabetic cognitive impairments. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Zhou, Wanqing AU - Zhou W AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China. FAU - Wang, Zhihua AU - Wang Z AD - , Department of Anesthesiology, Hainan General Hospital, Haikou, Hainan Province, China. FAU - Tao, Yuanyuan AU - Tao Y AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China. FAU - Chen, Cheng AU - Chen C AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China. FAU - Zhang, Qian AU - Zhang Q AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China. FAU - Liu, Zhuoyi AU - Liu Z AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China; , National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, Hunan Province, China. FAU - Li, Longyan AU - Li L AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China; , National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, Hunan Province, China. FAU - Xia, Pingping AU - Xia P AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China; , National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, Hunan Province, China. FAU - Ye, Zhi AU - Ye Z AD - , Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan Province, China; , National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, Hunan Province, China. Electronic address: yezhi523@csu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220823 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Annexin A2) RN - 0 (HSP90 Heat-Shock Proteins) RN - 0 (MEG3 non-coding RNA, rat) RN - 0 (Plectin) RN - 0 (RNA, Long Noncoding) RN - 2ZD004190S (Threonine) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - *Annexin A2/metabolism MH - Apoptosis MH - *Diabetes Mellitus, Experimental/genetics MH - Glucose/pharmacology MH - HSP90 Heat-Shock Proteins/metabolism MH - Hippocampus/metabolism MH - *Hyperglycemia/genetics MH - Neurons/metabolism MH - Plectin MH - RNA, Long Noncoding/*genetics/metabolism MH - Rats MH - Threonine/pharmacology OTO - NOTNLM OT - Diabetic cognitive impairments OT - HSP90A OT - Hyperglycemia OT - LncRNA-MEG3 OT - Mitochondrial functions COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/08/24 06:00 MHDA- 2022/09/14 06:00 CRDT- 2022/08/23 19:22 PHST- 2022/04/20 00:00 [received] PHST- 2022/08/09 00:00 [revised] PHST- 2022/08/10 00:00 [accepted] PHST- 2022/08/24 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/08/23 19:22 [entrez] AID - S0014-4827(22)00313-5 [pii] AID - 10.1016/j.yexcr.2022.113320 [doi] PST - ppublish SO - Exp Cell Res. 2022 Oct 15;419(2):113320. doi: 10.1016/j.yexcr.2022.113320. Epub 2022 Aug 23.