Effect of α1-adrenergic signaling pathway on doxorubicin-induced apoptosis in cardiomyocytes
10.3969/j.issn.1674-8115.2019.03.003
- Author:
Yu-Jiao YE
1
Author Information
1. Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Cardiomyocyte;
Doxorubicin;
Phenylephrine;
Prazosin
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2019;39(3):233-238
- CountryChina
- Language:Chinese
-
Abstract:
Objective • To investigate the effects of α1-adrenergic receptor agonist phenylephrine (Phe) and antagonist prazosin (Pra) on cardiomyocyte apoptosis induced by doxorubicin (DOX). Methods • H9C2 cardiomyocytes were divided into 4 groups. Except for the control group incubated with medium alone, all other groups were treated with 1.8 μmol/L DOX. For agonist group and antagonist group, 0.1 mmol/L Phe and 10 μmol/L Pra were added respectively in DOX-treated cells. After culture for 24 h, flow cytometry and TUNEL assay were performed to detect the apoptosis rate. Western blotting was used to detect the expression of cleaved caspase 3. Real-time PCR was used to detect the expression of anti- and pro-apoptotic Bcl-2 family genes. CCK-8 assay was used to detect the cell viability. Results • The DOX-induced apoptosis was inhibited by Phe with decreased apoptosis rate of H9C2 and decreased expression of cleaved caspase 3, but promoted by Pra. Increased expression of Bcl-2 and Bcl-w and decreasedexpression of Bax and Bad at mRNA levels were found in agonist group in comparison with the cells treated with DOX alone; while decreased expression of Bcl-2 and Bcl-w and increased expression of Bax and Bad were found in antagonist group. The cell viability after 24 h of treatment with agonist was higher than cells treated with DOX alone, but no signifiant difference was found in cell viability between antagonist group and DOX group. Conclusion • α1-Adrenergic signaling pathway may be involved in endogenous myocardial protection in the process of cardiomyocyte apoptosis induced by DOX.
