Role of losartan in angiotensin Ⅱ-induced oxidative stress in rat renal tubular epithelial cells
10.3760/cma.j.issn.1001-7097.2009.03.010
- VernacularTitle:氯沙坦对血管紧张素Ⅱ诱导大鼠肾小管上皮细胞氧化应激反应的作用
- Author:
Zhangzhe PENG
;
Lijian TAO
;
Ling WANG
;
Wangbin NING
;
Yanyun XIE
;
Nasui WANG
;
Bingxin LI
;
Yiting TANG
- Publication Type:Journal Article
- Keywords:
Losartan;
NADPH oxidase;
Reactive oxygen species;
Fibrosis;
Transforming growth factor betal;
Angiotensin Ⅱ
- From:
Chinese Journal of Nephrology
2009;25(3):204-209
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of losartan on angiotensin (Ang)Ⅱ-induced the generation of oxidative stress and expression of transforming growth factor β1(TGF-β1) in rat proximal tubular epithelial cells and to explore its underlying mechanism. MethodsNRK-52E cells, a rat proximal tubular epithelial cell line, were applied to explore the antioxidationand antifibrosis of losartan. The expression of three subunits of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, including p47phox, Nox-4, p22phox, and TGF-β1 were determined by real-time RT-PCR and/or Western blot. The generation of reactive oxygen species (ROS) was measured by DCF fluorescence analysis. Superoxide dismutase (SOD) in the supernatant was measured by colorimetric method. Results10-7 mol/L Ang Ⅱ up-regulated p22prox, p47phox and Nox-4 mRNA and protein expression, and the mRNA increased by 5.57-fold, 5.55-fold and 9.41-fold at 24 h (P<0.01, respectively) and the protein increased by 4.53-fold, 4.17-fold and 6.50-fold at 24 h (P<0.01, respectively) as compared with control. Losartan greatly reduced the mRNA elevation of p22prox, p47phox and Nox-4 by 2.71-fold, 2.18-fold and 5.23-fold (P<0.01, respectively) and reduced the protein elevation by 3.20-fold, 2.30-fold and 4.30-fold (P<0.01, respectively) as compared with control. Losartan also inhibited ROS generation induced by Ang Ⅱ in rat proximal tubular epithelial cells. SOD level in the supernatant was markedly decreased after Ang Ⅱ stimulation, while losartan could increase SOD levels (P<0.01). Furthermore, losartan signficantly inhibited Ang Ⅱ-induced TGF-β1 mRNA up-regulation by 64% (P<0.01). ConclusionsLosartan acts as an anti-oxidative and anti-fibrotic agent via the mechanisms of blocking NADPH oxidase-dependent oxidative stress and inhibiting TGF-β1 expression.
