GSK3β and MCL-1 mediate cardiomyocyte apoptosis in response to high glucose
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Gestational diabetes mellitus is a risk factor for congenital heart defects. Our previous results indicated that a decrease in myocardial cells and an increase in apoptotic cells leads to heart defects under hyperglycemia, but much work remains to elucidate this important mechanism of myocardial cell apoptosis induced by high glucose (HG). In this study, we found that a decrease in GSK3β phosphorylation on Ser9 occurred concomitantly with HG-induced cardiomyocyte apoptosis and in the heart tissues of the offspring of diabetic rats in vitro and in vivo. Decreases in GSK3β (Ser9) phosphorylation in response to HG were remarkably restored after treatment with SC79, an activator of the Akt signaling pathway. SB216763, an effective inhibitor of the GSK3β signaling pathway, suppressed HG-induced apoptosis in cardiomyocytes. Further studies showed a decrease in the expression of the anti-apoptotic protein MCL-1 was associated with GSK3β-mediated apoptosis. MCL-1 overexpression partly inhibits HG-induced apoptosis in cardiomyocytes. Herein, this study revealed the roles of GSK3β and MCL-1 in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced abnormalities.
KeywordsCardiomyocyte apoptosis Congenital heart disease High glucose GSK3β MCL-1
We are grateful to everyone who helped complete this research successfully. We especially, thank professor Ma for supporting the research and Lina Guan, who helped us in many experiments.
This research was supported by grants from the National Natural Science Foundation of China (Grant No. 31871391), the Central Public interest Scientific Institution Basal Research Fund (Grant No. 2018GJZ01), and the National Key Research and Development Program of China (Grant No. 2016YFC1000307, YCZYPT ).
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Conflict of interest
We declare that there are no conflicts of interests.
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