Abstract
BackgroundSIRT3, a member of the sirtuin family of NAD+-dependent deacetylases, resides primarily in the mitochondria and has been shown to deacetylate several metabolic and respiratory enzymes that regulate important mitochondrial functions. Previous researches show an important role of SIRT3 in regulating the production of reactive oxygen species (ROS), and highlight the ability of SIRT3 to protect cells from oxidative damage. A key substance of renin-angiotensin-aldosterone system (RAAS), Angiotensin II (AngII) can induce cells dysfunction by increasing the production of ROS. In this paper, we focus on the role of SIRT3 in AngII-induced human umbilical vein endothelial cells (HUVECs) dysfunction.MethodsTo study the influence of AngII on SIRT3 expression, HUVECs were treated with AngII of 10−7, 10−6, 10−5 mol/L for 24 h. SIRT3 expression was detected by wester-blotting analysis and RT-PCR. In addition, to research the role of SIRT3 in AngII-induced HUVECs,we used SIRT3 siRNA to knock down SIRT3 expression in HUVECs. Cells pretreated with negative control siRNA or SIRT3 siRNA were exposed to AngII for 24 h, and endothelial nitric oxide synthase (eNOS) expression, eNOS activity, total level of nitric oxide (NO) and ROS generation of each group were detected.ResultsHere we show that AngII treatment could increase generation of ROS, and decrease eNOS activity and total level of NO, while upregulated eNOS expression as a compensatory mechanism. The stimulation of AngII upregulated the expression of SIRT3 in HUVECs. SIRT3 siRNA worsen the AngII-induced effects above, besides, downregulated eNOS protein expression.ConclusionThese data suggest that SIRT3 plays a role of protection in AngII-induced HUVECs dysfunction via regulation of ROS generation.
Highlights
SIRT3, a member of the sirtuin family of NAD+-dependent deacetylases, resides primarily in the mitochondria and has been shown to deacetylate several metabolic and respiratory enzymes that regulate important mitochondrial functions
We investigated the influence of Angiotensin II (AngII) on the protein expression of SIRT3 in human umbilical vein endothelial cells (HUVECs) and the role of SIRT3 in AngII-induced HUVECs dysfunction
Dose-dependent effects of AngII on SIRT3 expression of HUVECS Treatment with 0, 10−7, 10−6, 10−5 mol/L AngII for 24 h resulted in a significant increase of SIRT3 protein expression in HUVECS, with the peak at 10−6 mol/L (Fig. 1a and b)
Summary
SIRT3, a member of the sirtuin family of NAD+-dependent deacetylases, resides primarily in the mitochondria and has been shown to deacetylate several metabolic and respiratory enzymes that regulate important mitochondrial functions. A key substance of renin-angiotensin-aldosterone system (RAAS), Angiotensin II (AngII) can induce cells dysfunction by increasing the production of ROS. To research the role of SIRT3 in AngII-induced HUVECs,we used SIRT3 siRNA to knock down SIRT3 expression in HUVECs. Cells pretreated with negative control siRNA or SIRT3 siRNA were exposed to AngII for 24 h, and endothelial nitric oxide synthase (eNOS) expression, eNOS activity, total level of nitric oxide (NO) and ROS generation of each group were detected. Endothelial dysfunction, mainly refer to an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide (NO) bioactivity in the vessel wall, is observed in the presence of major cardiovascular risk factors, including atherosclerosis, hypertension, and heart failure [1,2,3]. Oxidative stress (OS) contributes to vascular injury by promoting inflammation, endothelial dysfunction and increased vascular tone, leading to altered vascular contractility, structural remodeling, and hypertension as well as other forms of cardiovascular disease [12]
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