Abstract
BackgroundSevoflurane postconditioning (SpostC) can alleviate hypoxia-reoxygenation injury of cardiomyocytes; however, the specific mechanism remains unclear. This study aimed to investigate whether SpostC promotes mitochondrial autophagy through the hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) signaling pathway to attenuate hypoxia-reoxygenation injury in cardiomyocytes.MethodsThe H9C2 cardiomyocyte hypoxia/reoxygenation model was established and treated with 2.4% sevoflurane at the beginning of reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis. Mitochondrial ultrastructural and autophagosomes were observed by transmission electron microscope. Western blotting was used to examine the expression of HIF-1, BNIP3, and Beclin-1 proteins. The effects of BNIP3 on promoting autophagy were determined using interfering RNA technology to silence BNIP3.ResultsHypoxia-reoxygenation injury led to accumulation of autophagosomes in cardiomyocytes, and cell viability was significantly reduced, which seriously damaged cells. Sevoflurane postconditioning could upregulate HIF-1α and BNIP3 protein expression, promote autophagosome clearance, and reduce cell damage. However, these protective effects were inhibited by 2-methoxyestradiol or sinBNIP3.ConclusionSevoflurane postconditioning can alleviate hypoxia-reoxygenation injury in cardiomyocytes, and this effect may be achieved by promoting mitochondrial autophagy through the HIF-1/BNIP3 signaling pathway.
Highlights
Oxidative phosphorylation generates energy in mitochondria in cardiomyocytes
sevoflurane postconditioning (SpostC) alleviated cell injury induced by hypoxia and reoxygenation Cell viability, lactate dehydrogenase (LDH) activity, and apoptosis reflect the extent of cell damage
The LDH assay showed that compared to the control group, the LDH activity of the Hypoxia-reoxygenation group (H/R) group was increased (P < 0.05), while the LDH activity of the SpostC group was decreased compared to the H/R group (P < 0.05) (Fig. 3B)
Summary
Oxidative phosphorylation generates energy in mitochondria in cardiomyocytes. Functionally intact mitochondria are important for the heart to maintain physiological activities. It can selectively remove damaged mitochondria that are aged or excessively producing ROS through autophagy and promote mitochondrial renewal and recycling to ensure stable mitochondrial function and promote cell survival (Mizushima & Komatsu, 2011). At present, this adaptive metabolic mechanism has attracted much attention in the field of hypoxic stress. Sevoflurane postconditioning could upregulate HIF-1a and BNIP3 protein expression, promote autophagosome clearance, and reduce cell damage These protective effects were inhibited by 2-methoxyestradiol or sinBNIP3. Conclusion: Sevoflurane postconditioning can alleviate hypoxia-reoxygenation injury in cardiomyocytes, and this effect may be achieved by promoting mitochondrial autophagy through the HIF-1/BNIP3 signaling pathway
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