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Histochemistry and Cell Biology

, Volume 152, Issue 3, pp 217–225 | Cite as

GSK3β and MCL-1 mediate cardiomyocyte apoptosis in response to high glucose

  • Dongmei Su
  • Jing Zhao
  • Shanshan Hu
  • Lina Guan
  • Qian Li
  • Cuige Shi
  • Xu MaEmail author
  • Jianjun GouEmail author
  • Yunjun ZhouEmail author
Original Paper
  • 161 Downloads

Abstract

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.

Keywords

Cardiomyocyte apoptosis Congenital heart disease High glucose GSK3β MCL-1 

Notes

Acknowledgements

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.

Funding

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 [2018]).

Compliance with ethical standards

Conflict of interest

We declare that there are no conflicts of interests.

Supplementary material

418_2019_1798_MOESM1_ESM.pdf (138 kb)
Supplementary material 1 (PDF 137 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Genetics, Center for Genetics, Health DepartmentNational Research Institute for Family PlanningBeijingChina
  2. 2.Graduate SchoolPeking Union Medical CollegeBeijingChina
  3. 3.Department of CardiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  4. 4.Hongqi Hospital of Mudanjiang Medical CollegeMudanjiangChina

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