Effect of 5-AZA-2'-dC on angiotensin Ⅱ-induced cardiomyocyte hypertrophy
10.3760/cma.j.issn.1671-0282.2018.03.014
- VernacularTitle:5-氮杂胞苷抑制血管紧张素Ⅱ诱导心肌肥大的作用研究
- Author:
Meiting CHEN
1
;
Yi ZHANG
;
Huilin JIANG
;
Peiyi LIN
;
Xiaohui CHEN
Author Information
1. 广州医科大学附属第二医院急诊科
- Keywords:
Cardiomyocyte hypertrophy;
Methylation inhibitor;
5-AZA-2'-dC;
Angiotensin Ⅱ;
Sarcoplasmic reticulum Ca2+ ATPase
- From:Chinese Journal of Emergency Medicine
2018;27(3):301-306
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of 5-AZA-2'-dC on Angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy.Methods Cultured cells derived from neonatal heart of rat were divided into 5 groups:normal control,hypertrophic group,5-AZA-2'-dC treatment group,and 5-AZA-2'-dC pretreatment group.Neonatal rat cardiomyocyte hypertrophic response was assayed by the size of cardiomyocytes and atrial natriuretic polypeptide (ANP) expressive level.The level of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a),total calmodulin kinase Ⅱ (CaMK Ⅱ) and phospho-CaMK Ⅱ (p-CaMK Ⅱ) detected by Western blot.The intracellular calcium changes of cardiomyocytes were imaged by confocal fluorescent microscopy.Results Cells treated with Ang Ⅱ at 10-6 mol/L for 48 h were chosen as hypertrophic cardiomyocyte model.The mRNA expression and protein level of ANP were significantly decreased in the treatment and pretreatment groups compared with hypertrophic group.The protein level of SERCA2a was significantly decreased in the hypertrophic group,and increased in the treatment and pretreatment group compared with hypertrophic group.The protein level of SERCA2a was significantly decreased in the hypertrophic group,and increased in the treatment and pretreatment group compared with hypertrophic group,whereas phospho-CaMK Ⅱ showed an opposite change tendency.The time required for increasing and declining to half of the intracellular calcium peak value were both delayed in hypertrophic group,as the treatment and pretreatment groups showed shorter time required compared with hypertrophic group.Conclusion 5-AZA-2'-dC could inhibit Ang Ⅱ-induced cardiomyocyte hypertrophy which might be related to regulate SERCA2a expression.Increased SERCA2a expression may maintain the calcium homeostasis through shortening the time of transfer Ca2+ from the cytosol of the cell to the lumen of the sarcoplasmic reticulum.
