Propofol Ameliorates H9c2 Cells Apoptosis Induced by Oxygen Glucose Deprivation and Reperfusion Injury via Inhibiting High Levels of Mitochondrial Fusion and Fission

Lidong Zhao; Jinqiang Zhuang; Yihui Wang; Dandan Zhou; Dandan Zhao; Shun Zhu; Jinjun Pu; Hongyu Zhang; Ming Yin; Wenjuan Zhao; Zejian Wang; Jiang Hong

doi:10.3389/fphar.2019.00061

Propofol Ameliorates H9c2 Cells Apoptosis Induced by Oxygen Glucose Deprivation and Reperfusion Injury via Inhibiting High Levels of Mitochondrial Fusion and Fission

Front Pharmacol. 2019 Feb 12:10:61. doi: 10.3389/fphar.2019.00061. eCollection 2019.

Authors

Lidong Zhao¹, Jinqiang Zhuang¹, Yihui Wang¹, Dandan Zhou¹, Dandan Zhao¹, Shun Zhu¹, Jinjun Pu², Hongyu Zhang³, Ming Yin⁴, Wenjuan Zhao⁴, Zejian Wang⁴, Jiang Hong¹

Affiliations

¹ Department of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Originally Named "Shanghai First People' s Hospital"), Shanghai, China.
² Department of Emergency Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Department of Biomedicine, KG Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway.
⁴ School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Background: The cardioprotective effect of propofol on ischemia-reperfusion injury (I/R injury) is partly due to suppressing apoptosis. Mitochondrial dynamics are also involved in apoptosis. Mitochondrial fusion and fission lead to mitochondrial morphological changes. However, whether suppressing apoptosis effect of propofol against ischemia-reperfusion injury in the heart is via regulating mitochondrial morphology remains unclear. Methods: H9c2 cells underwent oxygen glucose deprivation (OGD) followed by reperfusion to simulate cardiomyocytes ischemia/reperfusion injury. Cell viability, apoptosis ratio and intracellular reactive oxygen species (ROS) were assessed, respectively. Mitochondrial membrane dynamin family proteins, extracellular signal regulated kinase 1 and 2 (ERK1/2), phosphorylated extracellular signal regulated kinase 1 and 2 (p-ERK1/2) and proteins related to intrinsic apoptosis pathways were detected by western blotting. The mitochondrial morphology and the distribution of dynamin-related protein 1 (Drp1) were observed by using laser confocal microscopy. Results: Propofol enhanced the survival of H9c2 cells, decreased ROS levels and inhibited apoptosis during oxygen glucose deprivation/reperfusion (OGD/R) injury. Mitochondrial fission in H9c2 cells was inhibited by propofol during OGD injury. Propofol alleviated high levels of mitochondrial fusion and fission during OGD/R in H9c2 cells, by regulating mitochondrial membrane remodeling dynamin family proteins. Propofol inhibited Drp1 colocalization with mitochondria in H9c2 cells during OGD/R injury. Moreover, Drp1 phosphorylation was inhibited by propofol through decreasing ERK activation during OGD/R injury. We found that propofol ameliorated H9c2 cells apoptosis during OGD/R via inhibiting mitochondrial cytochrome c release and caspase-9, caspase-6, caspase-7 and caspase-3 activation. Conclusion: Propofol suppresses H9c2 cells apoptosis during OGD/R injury via inhibiting intrinsic apoptosis pathway, which may be partly due to reducing high levels of mitochondrial fusion and fission induced by OGD/R injury.

Keywords: apoptosis; ischemia; mitochondrial dynamics; propofol; reperfusion.