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首页> 外文期刊>American Journal of Nephrology >Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells.
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Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells.

机译:硫酸吲哚酚通过诱导血管内皮细胞的氧化应激而抑制一氧化氮的产生和细胞活力。

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BACKGROUND/AIM: Cardiovascular disease is a major cause of mortality in chronic kidney disease patients. Oxidative stress and nitric oxide (NO) deficiency play an important role in vascular endothelial cell dysfunction in chronic kidney disease. To determine if the uremic toxin indoxyl sulfate (IS) induces oxidative stress and inhibits NO production and cell viability in human umbilical vein endothelial cells (HUVEC). METHODS: The production of reactive oxygen species (ROS), superoxide, NO and peroxynitrite was measured using a fluorescence microplate reader. The expression of NADPH oxidases (Nox4, Nox2) was analyzed by quantitative reverse transcription-polymerase chain reaction. Cell viability was examined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate assay. RESULTS: IS induced ROS generation in HUVEC. An inhibitor of NADPH oxidase showed an inhibitory effect on IS-induced ROS production. However, the inhibitors of xanthine oxidase, mitochondrial electron transport and NO synthase did not show any significant effect on IS-induced ROS production. Antioxidants such as vitamin E, N-acetyl-L-cysteine and vitamin C inhibited IS-induced ROS production. IS induced the expression of Nox4 mRNA and the production of superoxide and peroxynitrite in HUVEC. IS inhibited NO production in HUVEC. IS inhibited cell viability, and antioxidants preserve the inhibitory effect of IS on cell viability. CONCLUSIONS: IS inhibits NO production and cell viability by inducing ROS through induction of Nox4 in HUVEC.
机译:背景/目的:心血管疾病是慢性肾脏疾病患者死亡的主要原因。氧化应激和一氧化氮(NO)缺乏在慢性肾脏疾病的血管内皮细胞功能障碍中起重要作用。要确定尿毒症毒素吲哚酚硫酸盐(IS)是否在人脐静脉内皮细胞(HUVEC)中诱导氧化应激并抑制NO产生和细胞活力。方法:使用荧光酶标仪检测活性氧(ROS),超氧化物,一氧化氮和过氧亚硝酸盐的产生。通过定量逆转录-聚合酶链反应分析NADPH氧化酶(Nox4,Nox2)的表达。通过4- [3-(4-碘苯基)-2-(4-硝基苯基)-2H-5-四唑基] -1,3-苯二磺酸盐测定法检查细胞活力。结果:IS诱导HUVEC产生ROS。 NADPH氧化酶的抑制剂显示出对IS诱导的ROS产生的抑制作用。然而,黄嘌呤氧化酶,线粒体电子运输和一氧化氮合酶的抑制剂对IS诱导的ROS产生没有显着影响。维生素E,N-乙酰基-L-半胱氨酸和维生素C等抗氧化剂可抑制IS诱导的ROS产生。 IS诱导HUVEC中Nox4 mRNA的表达以及过氧化物和过氧亚硝酸盐的产生。 IS抑制了HUVEC中的NO生成。 IS抑制了细胞活力,抗氧化剂保留了IS对细胞活力的抑制作用。结论:IS通过诱导HUVEC中的Nox4诱导ROS抑制NO的产生和细胞活力。

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