PMID- 33391885 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220419 IS - 2167-8359 (Print) IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 8 DP - 2020 TI - Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway. PG - e10603 LID - 10.7717/peerj.10603 [doi] LID - e10603 AB - BACKGROUND: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning (IPC). However, the underlying molecular mechanism of SPC remains unclear. Studies confirm that hypoxia-inducible factor-1 (HIF-1) can transform cells from aerobic oxidation to anaerobic glycolysis by activating the switch protein pyruvate dehydrogenase kinase-1 (PDK-1), thus providing energy for the normal life activities of cells under hypoxic conditions. The purpose of this study was to investigate whether the cardioprotective effects of SPC are associated with activation of the HIF-1a/PDK-1 signal pathway. METHODS: The H9c2 cardiomyocytes hypoxia/reoxygenation model was established and treated with 2.4% sevoflurane at the end of equilibration. Lactate dehydrogenase (LDH) level, cell viability, cell apoptosis, mitochondrial membrane potential, key enzymes of glycolysis, ATP concentration of glycolysis were assessed after the intervention. Apoptosis related protein(Bcl-2, Bax), HIF-1a protein, and PDK-1 protein were assessed by western blot. RESULTS: Compared with the H/R group, SPC significantly increased the expression of HIF-1a, PDK-1, and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the apoptosis ratio and Lactate dehydrogenase (LDH) level, increasing the cell viability, content of key enzymes of glycolysis, ATP concentration of glycolysis and stabilizing the mitochondrial membrane potential. However, the cardioprotective effects of SPC were disappeared by treatment with a HIF-1a selective inhibitor. CONCLUSION: This study demonstrates that the cardioprotective effects of SPC are associated with the activation of the HIF-1a/PDK-1 signaling pathway. The mechanism may be related to increasing the content of key enzymes and ATP of glycolysis in the early stage of hypoxia. CI - (c)2020 Hou et al. FAU - Hou, Tianliang AU - Hou T AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Ma, Haiping AU - Ma H AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Wang, Haixia AU - Wang H AD - Department of Mastology, Xinjiang Maternal and Child Health Hospital, Urumqi, Xinjiang, China. FAU - Chen, Chunling AU - Chen C AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Ye, Jianrong AU - Ye J AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Ahmed, Ahmed Mohamed AU - Ahmed AM AD - Department of Intensive Care Unit (ICU), Yardimeli Hospital, Mogadishu, Somalia. FAU - Zheng, Hong AU - Zheng H AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. LA - eng PT - Journal Article DEP - 20201221 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 PMC - PMC7759118 OTO - NOTNLM OT - Glycolysis OT - Hypoxia-inducible factor-1 OT - Hypoxia/reoxygenation injury OT - Myocardial protective effect OT - Pyruvate dehydrogenase kinase-1 OT - Sevoflurane preconditioning COIS- The authors declare there are no competing interests. EDAT- 2021/01/05 06:00 MHDA- 2021/01/05 06:01 PMCR- 2020/12/21 CRDT- 2021/01/04 05:29 PHST- 2020/09/03 00:00 [received] PHST- 2020/11/28 00:00 [accepted] PHST- 2021/01/04 05:29 [entrez] PHST- 2021/01/05 06:00 [pubmed] PHST- 2021/01/05 06:01 [medline] PHST- 2020/12/21 00:00 [pmc-release] AID - 10603 [pii] AID - 10.7717/peerj.10603 [doi] PST - epublish SO - PeerJ. 2020 Dec 21;8:e10603. doi: 10.7717/peerj.10603. eCollection 2020.