Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 2, pp 189–198 | Cite as

Heme oxygenase-1 ameliorates hypoxia/reoxygenation via suppressing apoptosis and enhancing autophagy and cell proliferation though Sirt3 signaling pathway in H9c2 cells

  • Xiangli Meng
  • Yuxiang Yuan
  • Fengjuan ShenEmail author
  • Chengqiu LiEmail author
Original Article


Cardiomyocyte infarction could lead to high morbidity and mortality worldwide. Recent studies demonstrated that Heme oxygenase-1 (HO-1) could exert cardiac protective effect and arouse attention. However, the detailed mechanism is still unclear. Our study provided evidences of the protective effect of HO-1 overexpression on cardiomyocytes against hypoxia/reoxygenation (H/R). We divided the treatment into four groups: the control group, H/R group, H/R+HO-1 group, and H/R+Null group. Immunofluorescent study was utilized to label the BrdU-positive and LC3-positive cells. Flow cytometry and TUNEL assay were used to examine the cell apoptosis. Protein levels of Bax, Bcl-2, Sirt3, beclin-1, LC3-I, and LC3-II were both measured using western blotting. The results indicated that HO-1 overexpression decreased the cell apoptosis and enhanced the cell proliferation. The level of Sirt3 and autophagy were also increased in H/R+HO-1 group compared with H/R group. However, ZnPP, a HO-1 inhibitor, and SiRNA of Sirt3 are both reversed the decrease of cell apoptosis of HO-1 overexpression. Moreover, ZnPP also decreased the expression of Sirt3 in HO-1 overexpression treatment group. In summary, HO-1 overexpression protects cardiomyocytes against H/R injury via ameliorating cell apoptosis and enhancing cell proliferation and autophagy through Sirt3 signaling pathway.


HO-1 Cardiomyocyte H/R Autophagy Apoptosis Proliferation 





Reactive oxygen species




Heme oxygenase-1




Mitochondrial DNA


Light chain 3


Adenosine 5′-monophosphate (AMP)-activated protein kinase


Author contributions

F.S. designed the study. X.L., Y.Y., and C.L. performed the experiments and collected the data. C.L. and F.S. analyzed and interpreted the experimental data. F.S. and C.L. prepared the manuscript.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Emergency departmentThe Zoucheng People’s HospitalJiningPeople’s Republic of China
  2. 2.Department of Cardiovascular MedicineThe Zoucheng People’s HospitalJiningPeople’s Republic of China

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