期刊
JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
卷 39, 期 4, 页码 341-349出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10799893.2019.1684521
关键词
Sirt3; PGC1 alpha; AMPK; mitochondria; cell death; caspase-9
资金
- Science and Technology Commission of Shanghai Municipality (STCSM) [17401934800]
- Health and Family Planning Commission of Minhang district of Shanghai [2017MW23]
- Cultivation project of National Natural Science Foundation from South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University [H0215]
Context: Sirtuin-3 (Sirt3), a NAD-dependent deacetylase, has been reported to be involved in many biological processes. Objective: The present study aimed to investigate the effect and mechanism of Sirt3 on diabetic mice and human umbilical vein endothelial cells (HUVECs) under high glucose (HG) condition. Materials and methods: HUVECs were cultured under HG and inflammation pathway was determined via qPCR, western blots, and immunofluorescence. Results: Sirt3 expression was reduced in the progression of diabetic nephropathy. Overexpression of Sirt3 sustains renal function and retard the development of diabetic nephropathy. Mechanistically, Sirt3 overexpression attenuated hyperglycemia-mediated endothelial cells apoptosis in kidney. Besides, Sirt3 overexpression repressed oxidative injury and blocked caspase-9-related apoptosis pathway. Moreover, we found that Sirt3 overexpression was associated with AMPK activation and the latter elevates PGC1 alpha-related mitochondrial protective system, especially mitochondrial autophagy. Loss of opa1 and/or inhibition of AMPK could depress mitochondrial autophagy and exacerbates mitochondrial function, finally contributing to the death of human renal mesangial cells. Conclusions: Our results demonstrated the beneficial effects of Sirt3 in the progression of diabetic nephropathy. Increased Sirt3-activated AMPK pathway, augments PGC1 alpha-related mitochondrial protective system, sustained redox balance and closed caspase-9-involved apoptosis pathway in the setting of diabetic nephropathy.
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