17β-雌二醇抗心肌细胞氧化应激损伤的Nrf2/HO-1信号通路的分子机制
17β-estradiol protects H_9C_2 cardiomyocytes from H_2O_2-induced injury via Nrf2/HO-1 signaling pathway
作者:杨静;黎洁;卢长喜;郭爱华;刘长青;杨华;石慧武;牛若颖;
Author:
收稿日期: 年卷(期)页码:2013,28(05):-467-470
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:H2O2;H9C2细胞;17β-雌二醇;Nrf 2;HO-1;氧化应激
Key words:
基金项目:
中文摘要
目的观察17β-雌二醇(E2)对H2O2诱导的心肌细胞氧化应激损伤的保护作用,探讨其可能的分子机制。方法将细胞分为对照组、H2O2组、E2组、抑制剂组。用MTT法观察心肌细胞的活性;用Western Blot技术检测Nrf 2的蛋白表达;用RT-PCR技术观察Nrf 2下游靶基因HO-1的mRNA水平。结果 100μmol·L-1H2O2可使H9C2细胞活性显著下降,E2预处理可有效阻止H2O2诱导的心肌细胞损伤;Nrf 2的蛋白表达自E2和H2O2共同培育2 h时即显著高于对照组,6 h达到最高峰;E2也诱导了H2O2处理后H9C2细胞HO-1 mRNA水平及其蛋白表达的升高;ICI 182,780明显逆转了E2的心肌保护作用。结论 E2可有效降低H2O2诱导的心肌细胞损伤,Nrf 2/HO-1信号通路的上调可能是其重要的分子机制。
参考文献
[1]Ren G,Qiao HX,Yang J,et al.Protective effects of steroids fromAllium chinense against H2O2-induced oxidative stress in ratcardiac H9C2 cells[J].Phytother Res,2010,24(3):404-409.
[2]Wink DA,Cook JA,Pacelli R,et al.The effect of various nitricoxide-donor agents on hydrogen peroxide-mediated toxicity:Adirect correlation between nitric oxide formation and protection[J].Arch Biochem Biophys,1996,331:241-248.
[3]Urata Y,Ihara Y,Murata H,et al.17Beta-estradiol protectsagainst oxidative stress-induced cell death through the glutathi-one/glutaredoxin-dependent redox regulation of Akt in myocar-diac H9C2 cells[J].Biol Chem,2006,281(19):13092-13102.
[4]Ren G,Qiao HX,Yang J,et al.Protective effects of steroids fromAllium chinense against H2O2-induced oxidative stress in ratcardiac H9C2 cells[J].Phytother Res,2010,24(3):404-409.
[5]Chou HC,Chen YW,Lee TR,et al.Proteomics study of oxidativestress and Src kinase inhibition in H9C2 cardiomyocytes:A cellmodel of heart ischemia-reperfusion injury and treatment[J].Free Radic Biol Med,2010,49(1):96-108.
[6]Giddabasappa A,Bauler M,Yepuru M,et al.17-βestradiol pro-tects ARPE-19 cells from oxidative stress through estrogenreceptor-β[J].Invest Ophthalmol Vis Sci,2010,51(10):5278-5287.
[7]Sheu SS,Nauduri D,Anders MW.Targeting antioxidants to mito-chondria:A new therapeutic direction[J].Biochim Biophys Acta,2006,1762:256-265.
[8]Túnez I,Collado JA,Medina FJ,et al.Protective effect of carve-dilol on oxidative stress induced by okadaic acid in N1E-115cells[J].Pharmacol Res,2006,54(3):241-246.
[9]Urata Y,Ihara Y,Murata H,et al.17Beta-estradiol protectsagainst oxidative stress-induced cell death through the glutathi-one/glutaredoxin-dependent redox regulation of Akt in myocardi-ac H9C2 cells[J].J Biol Chem,2006,281(19):13092-13102.
【关闭】