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Pathol Res Pract. 2015 Dec;211(12):955-62. doi: 10.1016/j.prp.2015.09.018. Epub 2015 Sep 25.

NF45 inhibits cardiomyocyte apoptosis following myocardial ischemia-reperfusion injury.

Author information

1
Department of Pathogen Biology, Medical College, Nantong University, Nantong, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, China.
2
Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, China.
3
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, China.
4
Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, China. Electronic address: ntwx0513@163.com.
5
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, China. Electronic address: ntsjh0513@163.com.

Abstract

Cardiomyocyte apoptosis, which occurs during ischemia and reperfusion injury, can cause irreversible damage to cardiac function. There is accumulating evidence that nuclear factor 45 (NF45) and regulatory pathways are important in understanding reparative processes in the myocardium. NF45 is a multifunctional regulator of gene expression that participates in the regulation of DNA break repair. Recently, NF45 has been proved to be associated with tumor cell apoptosis in various human malignancies. However, the underlying mechanism of NF45 regulating myocardial ischemia-reperfusion (I/R) injury remains unclear. In this study, western blot showed that NF45 expression decreased after myocardial I/R in vivo. Double immunofluorescent staining revealed that NF45, located in the nucleus of cardiomyocyes, was correlated with cardiomyocyte apoptosis. Furthermore, NF45 expression decreased in H9c2 cells after hypoxia-reoxygenation (H/R) treatment in vitro, which was in line with the results in vivo. Overexpression of NF45 in H9c2 cells reduced cell apoptosis, as evidenced by increased Bcl-2 level, as well as decreased cleaved caspase-3, p53 and p21 expression. The expression of NF45 was reduced by LY294002 (a PI3K/Akt inhibitor), but not SB203580 (a p38 inhibitor), suggesting that NF45 prevented H/R-induced H9c2 cell apoptosis via PI3K/Akt pathway. Our data may supply a novel molecular target for acute myocardial infarction (AMI) therapy.

KEYWORDS:

Akt; Cardiomyocyte apoptosis; H9c2 cell; Myocardial ischemia–reperfusion; NF45

PMID:
26573128
DOI:
10.1016/j.prp.2015.09.018
[Indexed for MEDLINE]

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