自噬
压力过载
肌肉肥大
内科学
内分泌学
心肌肥大
基因剔除小鼠
心力衰竭
生物
医学
细胞生物学
细胞凋亡
生物化学
受体
作者
Rui‐De Xue,Jingzhou Jiang,Bin Dong,Weiping Tan,Yu Sun,Jingjing Zhao,Yili Chen,Yugang Dong,Chen Liu
标识
DOI:10.1016/j.abb.2017.09.012
摘要
Cardiac hypertrophy is the risk factor of heart failure when the heart is confronted with pressure overload or neurohumoral stimuli. Autophagy, a conserved degradative pathway, is one of the important mechanisms involved in the regulation of cardiac hypertrophy. DJ-1 is a traditional anti-oxidative protein and emerging evidence suggested that DJ-1 might modulate autophagy. However, the regulation of autophagy by DJ-1 in the process of cardiac hypertrophy remains unknown. In our study, we firstly discovered that the expression of DJ-1declined in the process of pressure overload cardiac hypertrophy, and its alteration was parallel with the impairment of autophagy. Furthermore, we proved that DJ-1 knockout mice exhibited a more hypertrophied phenotype than wildtype mice in cardiac hypertrophy which indicated that DJ-1 is responsible for the repression of cardiac hypertrophy. Furthermore, DJ-1 knockout significantly exacerbated pulmonary edema due to cardiac hypertrophy. In the process of cardiac hypertrophy, DJ-1 knockout significantly impaired autophagy activation and enhanced mTORC1 and mTORC2 phosphorylation were found. Similarly, our in vitro study proved that DJ-1 overexpression ameliorated phenylephrine (PE)-induced cardiac hypertrophy and promoted autophagy activation. Taken together, DJ-1 might repress both pressure overload and PE-induced cardiac hypertrophy via the activation of autophagy.
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