Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway

Tianliang Hou; Haiping Ma; Haixia Wang; Chunling Chen; Jianrong Ye; Ahmed Mohamed Ahmed; Hong Zheng

doi:10.7717/peerj.10603

Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway

PeerJ. 2020 Dec 21:8:e10603. doi: 10.7717/peerj.10603. eCollection 2020.

Authors

Tianliang Hou^#¹, Haiping Ma^#¹, Haixia Wang², Chunling Chen¹, Jianrong Ye¹, Ahmed Mohamed Ahmed³, Hong Zheng¹

Affiliations

¹ Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
² Department of Mastology, Xinjiang Maternal and Child Health Hospital, Urumqi, Xinjiang, China.
³ Department of Intensive Care Unit (ICU), Yardimeli Hospital, Mogadishu, Somalia.

^# Contributed equally.

Abstract

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.

Keywords: Glycolysis; Hypoxia-inducible factor-1; Hypoxia/reoxygenation injury; Myocardial protective effect; Pyruvate dehydrogenase kinase-1; Sevoflurane preconditioning.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. U1603129) and the National Natural Science Foundation of China (No. 81660522). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.