GATA4在Cr(Ⅵ)诱导肝细胞早衰中的作用研究  

The role of GATA4 in Cr(Ⅵ)-induced premature senescence in hepatocytes

作　　者：边寰锋 刘乐玫 李思文 苏莹 曾元 BIAN Huan-feng;LIU Le-mei;LI Si-wen;SU Ying;ZENG Yuan(Shenzhen Baoan district public health service Shajing Branch Center,Shenzhen,Guangdong 518000,China;Department of Health Toxicology,Xiangya School of Public Health,Central South University,Changsha,Hunan 410078,China)

机构地区：[1]深圳市宝安区公共卫生服务沙井分中心,广东深圳518000 [2]中南大学湘雅公共卫生学院卫生毒理系,湖南长沙410078

出　　处：《毒理学杂志》2024年第3期232-236,共5页Journal of Toxicology

基　　金：深圳市科技计划项目(JCYJ20180305163211804)。

摘　　要：目的通过构建Cr(Ⅵ)诱导的早衰L02肝细胞模型,研究GATA4在调控细胞早衰过程中所发挥的作用。方法10 nmol/L Cr(Ⅵ)连续处理L02肝细胞4周。采用β-Gal染色及Western blot检测衰老相关蛋白表达明确L02肝细胞早衰发生。通过慢病毒转染构建GATA4-sh L02肝细胞及其对照组Scr与并予以Cr(Ⅵ)染毒探讨GATA4对细胞衰老的作用。采用β-Gal染色及Western blot检测衰老相关蛋白表达明确GATA4能够促进Cr(Ⅵ)诱导L02肝细胞早衰。结果10 nmol/L Cr(Ⅵ)处理L02肝细胞4周后β-Gal染色呈现大量阳性衰老细胞且衰老相关蛋白FN1、CLU和SMP30表达明显升高(LSD-t=5.52,10.39,11.66,P<0.05)。GATA4/NF-κB通路相关蛋白GATA4、TRAF3IP2和p65表达明显升高(LSD-t=12.13,16.64,13.73,P<0.05)。当敲低GATA4后10 nmol/L Cr(Ⅵ)处理GATA4-sh L02肝细胞,与对照组相比衰老相关蛋白表达明显降低(t=15.30,P<0.05)。结论Cr(Ⅵ)通过GATA4诱导L02肝细胞早衰发生。Objective To investigate the role played by GATA4 in regulating premature senescence by constructing a Cr(Ⅵ)-induced prematurely senescent L02 hepatocyte model.Methods L02 hepatocytes were continuously treated with 10 nmol/L Cr(Ⅵ).β-Gal staining and Western blot were used to detect senescence-related protein expression to clarify the onset of premature senescence in L02 hepatocytes.The effect of GATA4 on cellular senescence was investigated by constructing GATA4-sh L02 hepatocytes and their control cells with Cr(Ⅵ)staining.β-Gal staining and Western blot were used to detect the expression of senescence-associated proteins,and it was clear that GATA4 could promote the premature senescence of L02 hepatocytes induced by Cr(Ⅵ).Results After 10 nmol/L Cr(Ⅵ)treatment of L02 hepatocytes for 4 weeks,β-Gal staining showed a large number of positive senescent cells and the expressions of senescence-related proteins FN1,CLU and SMP30 were significantly increased(LSD-t=5.52,10.39,11.66,P<0.05).The expressions of GATA4,TRAF3IP2 and p65,proteins related to GATA4/NF-κB pathway,were significantly increased(LSD-t=12.13,16.64,13.73,P<0.05).When GATA4 was knocked down after 10 nmol/L Cr(Ⅵ)treatment of GATA4-sh L02 hepatocytes,the expression of senescence-associated proteins was significantly lower compared with the control group(t=15.30,P<0.05).Conclusion Cr(Ⅵ)induces premature senescence in L02 hepatocytes via GATA4.

关 键 词：六价铬[Cr(Ⅵ)] 细胞早衰 锌指转录因子GATA4 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]