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白藜芦醇对组蛋白H3磷酸化、丝裂原活化蛋白激酶p38、沉默信息调节因子2(SIR 2)及p53表达的影响:在预防链脲佐菌素诱导的I型糖尿病肾病中的作用

Change in histone H3 phosphorylation, MAP kinase p38, SIR 2 and p53 expression by resveratrol in preventing streptozotocin induced type I diabetic nephropathy.

作者信息

Tikoo Kulbhushan, Singh Karmveer, Kabra Dhiraj, Sharma Vikram, Gaikwad Anil

机构信息

Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India.

出版信息

Free Radic Res. 2008 Apr;42(4):397-404. doi: 10.1080/10715760801998646.

Abstract

Resveratrol has been reported to have a wide variety of biological effects. However, little is known regarding its role on phosphorylation of histone H3, MAP kinase p38, SIR2 and p53 in type I diabetic nephropathy (DN). Hence, the present study was undertaken to examine changes in the above said parameters by resveratrol treatment. Male Sprague-Dawley rats were rendered diabetic using a single dose of streptozotocin (55 mg/kg, i.p.). DN was assessed by measurements of blood urea nitrogen and creatinine levels. Phosphorylation of histone H3, SIR2, p53 and MAP kinase p38 expression were examined by western blotting. This study reports that treatment of resveratrol prevents the decrease in the expression of SIR2 in diabetic kidney. It also prevents increase in p38, p53 expression and dephosphorylation of histone H3 in diabetic kidney. This is the first report which suggests that protection against development of diabetic nephropathy by resveratrol treatment involves change in phosphorylation of histone H3, expression of Sir-2, p53 and p38 in diabetic kidney.

摘要

据报道,白藜芦醇具有多种生物学效应。然而,关于其在I型糖尿病肾病(DN)中对组蛋白H3、丝裂原活化蛋白激酶p38、沉默信息调节因子2(SIR2)和p53磷酸化的作用,人们所知甚少。因此,本研究旨在通过白藜芦醇治疗来检测上述参数的变化。雄性Sprague-Dawley大鼠通过单次腹腔注射链脲佐菌素(55 mg/kg)诱导糖尿病。通过测量血尿素氮和肌酐水平评估糖尿病肾病。通过蛋白质免疫印迹法检测组蛋白H3、SIR2、p53的磷酸化以及丝裂原活化蛋白激酶p38的表达。本研究报告称,白藜芦醇治疗可防止糖尿病肾脏中SIR2表达的降低。它还可防止糖尿病肾脏中p38、p53表达的增加以及组蛋白H3的去磷酸化。这是第一份表明白藜芦醇治疗对糖尿病肾病发展的保护作用涉及糖尿病肾脏中组蛋白H3磷酸化、Sir-2、p53和p38表达变化的报告。

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