DJ-1 activates autophagy in the repression of cardiac hypertrophy
DJ-1 activates autophagy in the repression of cardiac hypertrophy
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DJ-1 激活自噬抑制心脏肥大
DOI：
10.1016/j.abb.2017.09.012
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Xue R;Jiang J;Dong B;Tan W;Sun Y;Zhao J;Chen Y;Dong Y;Liu C
当心脏面临压力超负荷或神经体液刺激时，心脏肥大是心力衰竭的危险因素。自噬是一种保守的降解途径，是参与调节心脏肥大的重要机制之一。 DJ-1 是一种传统的抗氧化蛋白，新的证据表明 DJ-1 可能调节自噬。然而，DJ-1在心脏肥大过程中对自噬的调节作用尚不清楚。本研究首次发现压力超负荷心肌肥厚过程中DJ-1表达下降，且其变化与自噬受损平行。此外，我们证明DJ-1敲除小鼠在心脏肥大方面表现出比野生型小鼠更肥厚的表型，这表明DJ-1负责抑制心脏肥大。此外，DJ-1敲除显着加剧了心脏肥大引起的肺水肿。在心脏肥大过程中，DJ-1敲除显着削弱了自噬激活，并增强了mTORC1和mTORC2磷酸化。同样，我们的体外研究证明，DJ-1 过表达可改善去氧肾上腺素 (PE) 诱导的心脏肥大并促进自噬激活。综上所述，DJ-1 可能通过激活自噬来抑制压力超负荷和 PE 引起的心脏肥大。
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.