类泛素蛋白FAT10:一个具有抵抗心肌细胞凋亡作用的新分子  

Ubiquitin-like protein modifier FAT10:a novel molecule that protects cardiac myocytes against apoptosis

作　　者：申阳[1] 邵江华[2] 彭小刚[3] 曹青[3] 刘秀霞[3] 贺文凤[3] 刘欣[1] 洪葵[1] 

机构地区：[1]南昌大学第二附属医院心内科,南昌330006 [2]南昌大学第二附属医院普外科 [3]江西省分子医学重点实验室

出　　处：《临床心血管病杂志》2014年第5期447-450,共4页Journal of Clinical Cardiology

基　　金：教育部创新团队基金(No:IRT1141);国家自然科学基金(No:81070148;81060196);国家重大基础研究973计划(No:2007CB512002;2008CB517305)

摘　　要：目的:确定FAT10在心肌细胞的表达及其在细胞凋亡中发挥的作用。方法:①提取大鼠、小鼠和人心脏组织总RNA与总蛋白,分别用RT-PCR与Western Blot检测FAT10的表达。②构建大鼠心肌梗死(心梗)模型与大鼠乳鼠原代心肌细胞缺氧/复氧(H/R)模型,分别用实时荧光定量PCR与Western Blot检测FAT10的表达变化。③体外构建FAT10过表达慢病毒,转染原代心肌细胞后暴露于H/R的环境中,通过流式细胞术检测心肌细胞凋亡率,用Western Blot检测凋亡相关蛋白Bcl-2与BAX的表达量。结果:FAT10的mRNA与蛋白在大鼠、小鼠和人的正常心脏组织中均有表达。在大鼠心梗模型的梗死心肌边缘区与H/R处理的大鼠原代心肌细胞中,FAT10表达量明显升高。在原代心肌细胞中过表达FAT10可以降低H/R引起的细胞凋亡,并且升高抗凋亡蛋白Bcl-2的表达,下调促凋亡蛋白BAX的表达。结论:FAT10是心肌组织表达的新蛋白,具有心脏保护作用,FAT10的表达上调能对抗心肌细胞凋亡。Objective：To determine the expression of FAT10in cardiac myocyte and the role of FAT10in apoptosis.Method：①Expression of FAT10in normal human and murine hearts was detected by RT-PCR and Western Blot.②Using myocardial infarction model in rats and cultured neonatal rat cardiac myocytes（NRCM） subjected to hypoxia/reoxygenation（H/R）stress,the change of FAT10expression was assessed by qRT-PCR and Western Blot.③After lentiviral-mediated overexpression of FAT10in NRCM,the apoptosis was assayed by flow cytometry and BCL-2,BAX expression level was also detected.Result：FAT10 was expressed in normal human and murine hearts.Lentiviral-mediated overexpression of FAT10in NRCM was associated with reduced apoptosis in response to H/R injury.Expression of FAT10was associated with increased anti-apoptotic protein Bcl-2level and reduced pro-apoptotic protein BAX level.Conclusion：FAT10is expressed in cardiac myocytes. Upregulation of FAT10protects cardiac myocytes against apoptosis by shifting the Bcl-2/Bax against apoptosis. Thus,FAT10is a cardioprotective gene and its upregulation might afford beneficial effects in pathological conditions associated with cardiac myocyte apoptosis.

关 键 词：FAT10 类泛素蛋白 心肌细胞 缺氧 细胞凋亡 

分 类 号：R541.4[医药卫生—心血管疾病]