Protective effect of SIRT1 on rat mesangial cells by decreasing high glu-cose-induced acetylation of NF-κB p65
10.3969/j.issn.1000-4718.2014.04.016
- VernacularTitle:SIRT1通过降低 NF-κB p65乙酰化减轻高糖应激引起的大鼠肾小球系膜细胞损伤
- Author:
Yueguang DU
;
Kefu CHAI
;
Junwen QIAN
;
Kena ZHANG
- Publication Type:Journal Article
- Keywords:
Silent information regulator 1;
NF-kappa B;
Inflammation;
Diabetic nephropathies
- From:
Chinese Journal of Pathophysiology
2014;33(4):664-669
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effects of silent information regulator 1 (SIRT1) on high glucose-induced acetylation of NF-κB p65 subunit and its protective role in rat mesangial cells .METHODS:Rat mesangial cells were cul-tured in DMEM supplemented with 10% FBS and were divided into control group , mannitol group , high glucose group , resveratrol group and SIRT1 RNAi group.The cell viability was determined by MTT assay .The mRNA expression of SIRT1, monocyte chemoattratant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1-1), tumor necrosis fac-torα( TNF-α) , transforming growth factor β1 ( TGF-β1 ) was analyzed by real-time quantitative PCR .The protein expres-sion of SIRT1 and the acetylation of NF-κB p65 subunit were determined by Western blotting .The protein concentrations of MCP-1, VCAM-1, TNF-α, TGF-β1 and malondialdehyde (MDA) were detected by ELISA.RESULTS:The cell viabili-ty, superoxide dismutase (SOD) activity, and the expression of SIRT1 at mRNA and protein levels were decreased by high glucose treatment as compared with control group .The acetylation of NF-κB p65 subunit was significantly increased after interfered with high glucose , resulting in the increase in the secretion of MCP-1, VCAM-1, TNF-αand TGF-β1 .Resvera-trol decreased high glucose-induced acetylation of NF-κB p65 subunit.However, silencing SIRT1 significantly enhanced the acetylation of NF-κB p65 subunit and the expression of MCP-1, VCAM-1, TNF-αand TGF-β1 .CONCLUSION:SIRT1 remarkably inhibits the inflammatory reactions by deacetylating NF-κB p65, suggesting that SIRT1 is a possible tar-get for preventing diabetic nephropathy .
