PMID- 29969626 OWN - NLM STAT- MEDLINE DCOM- 20190115 LR - 20211204 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 503 IP - 4 DP - 2018 Sep 18 TI - Gastrodin pretreatment alleviates myocardial ischemia/reperfusion injury through promoting autophagic flux. PG - 2421-2428 LID - S0006-291X(18)31490-6 [pii] LID - 10.1016/j.bbrc.2018.06.171 [doi] AB - Gastrodin (GAS), a monomeric component exacted from the herb Gastrodia elata Bl, may have cardioprotective effects during injury caused by myocardial ischemia/reperfusion (I/R). For the significant role of autophagy in I/R process, we targeted to explore whether autophagy was contributing to the GAS-induced protective effects during I/R procedure. Male C57BL/6 mice were subjected to reversible left coronary artery ligation and cultured neonatal rat cardiomyocytes (NRCs) exposed to hypoxia were preconditioned with GAS prior to ischemia or hypoxia, following reperfusion for 2 h or re-oxygennation for 3 h respectively. Our results demonstrated that GAS pretreatment increased autophagy and reduced apoptosis during I/R, this effect was weakened by co-treatment with the autophagic flux inhibitor chloroquine (Cq). Compared to mice subjected solely to I/R, GAS-pretreated mice had a notably smaller heart infarct size and an elevation in cardiac function. In GAS-pretreated NRCs, WB data showed that autophagy was promoted (expression of p62 was inhibited and LC3II was increased). In addition, tandem fluorescent mRFP-GFP-LC3 assays illustrated that autophagosomes were degraded duo to an increase in autophagic flux. Co-administration of Cq blocked the autophagic flux. Furthermore, GAS pretreatment increased the mitochondrial membrane potential of NRCs with subjected to H/R and increased the cardiomyocyte survival rate. These protective effects were reversed with Cq. Besides, GAS-induced the enhaucement of autophagy may correlated with activating AMP-activated protein kinase (AMPK) phosphorylation and reduced Mammalian target of rapamycin (mTOR) phosphorylation, which was abrogated by Compound C (Com C, AMPK-specific inhibitor). Our results establish that GAS pretreatment attenuates myocardial I/R injury by increasing autophagic flux aimed at eliminating dysfunctional mitochondria, therefore protecting neighbouring mitochondria and cardiomyocytes. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Fu, Shanshan AU - Fu S AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Chen, Linlin AU - Chen L AD - Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jianshe Road, 450052, Zhengzhou, China. FAU - Wu, Yizhang AU - Wu Y AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Tang, Ying AU - Tang Y AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Tang, Lu AU - Tang L AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Zhong, Yongkang AU - Zhong Y AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Wang, Siyi AU - Wang S AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Liu, Haiqiong AU - Liu H AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Wang, Xianbao AU - Wang X AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. FAU - Chen, Aihua AU - Chen A AD - Department of Cardiology, Heart Center, Zhujiang Hospital of Southern Medical University, NO. 253, Gongye Avenue, 510282, Guangzhou, China. Electronic address: zj_chenaihua@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180703 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Benzyl Alcohols) RN - 0 (Cardiotonic Agents) RN - 0 (Glucosides) RN - 5YS9U2W3RQ (gastrodin) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases) SB - IM MH - AMP-Activated Protein Kinase Kinases MH - Animals MH - Apoptosis/drug effects MH - Autophagy/*drug effects MH - Benzyl Alcohols/chemistry/*therapeutic use MH - Cardiotonic Agents/chemistry/*therapeutic use MH - Cells, Cultured MH - Gastrodia/chemistry MH - Glucosides/chemistry/*therapeutic use MH - Male MH - Membrane Potential, Mitochondrial/drug effects MH - Mice, Inbred C57BL MH - Myocardial Reperfusion Injury/*drug therapy/metabolism/pathology MH - Myocytes, Cardiac/*drug effects/metabolism/pathology MH - Phosphorylation/drug effects MH - Protein Kinases/metabolism MH - Rats MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - Apoptosis OT - Autophagy OT - Gastrodin OT - Ischemia/reperfusion OT - Mitochondrial function EDAT- 2018/07/04 06:00 MHDA- 2019/01/16 06:00 CRDT- 2018/07/04 06:00 PHST- 2018/06/16 00:00 [received] PHST- 2018/06/29 00:00 [accepted] PHST- 2018/07/04 06:00 [pubmed] PHST- 2019/01/16 06:00 [medline] PHST- 2018/07/04 06:00 [entrez] AID - S0006-291X(18)31490-6 [pii] AID - 10.1016/j.bbrc.2018.06.171 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Sep 18;503(4):2421-2428. doi: 10.1016/j.bbrc.2018.06.171. Epub 2018 Jul 3.