Study on the mechanism of Withaferin A enhancing hypoxia tolerance of cardiomyocytes
LI Mengchen
ZHAO Ruzhou
JIAO Bo
YU Zhibin
Abstract：Objective To determine the impact of Withaferin A(WA)on hypoxia tolerance in AC 16 cardiomyocytes and to elucidate its possible mechanism.Methods Cardiomyocytes were treated with WA for 48 h and then exposed to hypoxia for 24 h.Cell apoptosis rate was detected using flow cytometry.The effects of WA on the number and morphology of mitochondria as well as the distribution of glycogen particles in cardiomyocytes were observed by transmission electron microscopy.The expression levels of mitochondrial fusion and fission proteins and glycophagy-regulated proteins in cardiomyocytes were detected by Western blotting.Results The apoptosis rate of cardiomyocytes treated with WA decreased significantly under hypoxic conditions(P＜0.01).The number of mitochondria and the ratio of linear to granular mitochondria increased in WA-treated cardiomyocytes(P＜0.05).The expression level of mitochondrial fusion proteins in WA-treated cardiomyocytes increased(P＜0.05),but that of fission proteins decreased(P＜0.05).Obvious glycophagy could be observed,and the glycophagy-regulated proteins increased significantly in WA-treated cardiomyocytes(P＜0.05).Conclusion WA enhances hypoxia tolerance of cardiomyocytes via increasing mitochondrial fusion,inhibiting mitochondrial fission,and improving glycogen utilization.
Keywords：cardiomyocytehypoxia tolerancemitochondriamitofusin 1/2
Publication Date：2025-01-27
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)