Mitoquinone Protects Podocytes from Angiotensin II-Induced Mitochondrial Dysfunction and Injury via the Keap1-Nrf2 Signaling Pathway

被引:31
|
作者
Zhu, Zijing [1 ,2 ]
Liang, Wei [1 ,2 ]
Chen, Zhaowei [1 ,2 ]
Hu, Jijia [1 ,2 ]
Feng, Jun [1 ,2 ]
Cao, Yun [1 ,2 ]
Ma, Yiqiong [1 ,2 ]
Ding, Guohua [1 ,2 ]
机构
[1] Wuhan Univ, Div Nephrol, Renmin Hosp, Wuhan 430060, Peoples R China
[2] Wuhan Univ, Nephrol & Urol Res Inst, Wuhan 430060, Peoples R China
基金
美国国家科学基金会;
关键词
TRANSCRIPTION FACTOR NRF2; CHRONIC KIDNEY-DISEASE; SYSTEM; ACTIVATION; STRESS; PROGRESSION; MECHANISMS;
D O I
10.1155/2021/1394486
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Podocyte mitochondrial dysfunction plays a critical role in the pathogenesis of chronic kidney disease (CKD). Previous studies demonstrated that excessive mitochondrial fission could lead to the overproduction of reactive oxygen species (ROS) and promote podocyte apoptosis. Therefore, the maintenance of stable mitochondrial function is a newly identified way to protect podocytes and prevent the progression of CKD. As a mitochondria-targeted antioxidant, mitoquinone (MitoQ) has been proven to be a promising agent for the prevention of mitochondrial injury in cardiovascular disease and Parkinson's disease. The present study examined the effects of MitoQ on angiotensin II- (Ang II-) induced podocyte injury both in vivo and in vitro. Podocyte mitochondria in Ang II-infused mice exhibited morphological and functional alterations. The observed mitochondrial fragmentation and ROS production were alleviated with MitoQ treatment. In vitro, alterations in mitochondrial morphology and function in Ang II-stimulated podocytes, including mitochondrial membrane potential reduction, ROS overproduction, and adenosine triphosphate (ATP) deficiency, were significantly reversed by MitoQ. Moreover, MitoQ rescued the expression and translocation of Nrf2 (nuclear factor E2-related factor 2) and decreased the expression of Keap1 (Kelch-like ECH-associated protein 1) in Ang II-stimulated podocytes. Nrf2 knockdown partially blocked the protective effects of MitoQ on Ang II-induced mitochondrial fission and oxidative stress in podocytes. These results demonstrate that MitoQ exerts a protective effect in Ang II-induced mitochondrial injury in podocytes via the Keap1-Nrf2 signaling pathway.
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页数:22
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