NaDC3抑制人肾小管上皮细胞SIRT1的表达和活性  

NaDC3 inhibits expression and activity of SIRT1 in human kidney tubular epithelial cells

作　　者：刘维萍[1] 吴学敏[1] 张彦芬[1] 李涛[1] 郭永力[1] 管仁苹[1] 陈香美[2] 

机构地区：[1]河北省秦皇岛市第一医院肾内科,066000 [2]解放军总医院肾内科

出　　处：《中国药物与临床》2013年第11期1397-1401,I0002,共6页Chinese Remedies & Clinics

基　　金：国家重点基础研究发展973计划(2007cb507400)

摘　　要：目的探讨高亲和力钠依赖性二羧酸转运蛋白(NaDC3)加速肾脏衰老的作用机制。方法采用解放军总医院肾内科实验室构建的正反义NaDC3的逆转录病毒载体转染人肾小管上皮细胞系(HKC),通过调控NaDC3的表达水平,观察其对蛋白去乙酰化酶(SIRT1)mRNA、蛋白质表达和酶活性的影响。结果在HKC中NaDC3可通过增强能量代谢,降低尼克酰胺腺嘌呤二核苷酸(NAD)+/烟酰胺嘌呤二核苷酸还原态(NADH)的比值,抑制SIRT1的蛋白质表达和酶活性,即在转录后水平调控SIRT1。结论 NaDC3通过能量代谢调控SIRT1的活性加速肾脏衰老。Objective To explore the mechanism of NaDC3 leading to accelerated renal senescence.Methods The human renal tubular epithelial cell line （HKC） were transfected with sense/antisense NaDC3 retrovirus vectors constructed by Kidney Institute of Chinese People＇s Liberation Army for modulating the expression of NaDC3,thus allowed for the determination of the effects on SIRT1 mRNA and protein expression and enzyme activity.Results The NaDC3 promoted metabolism of energy and reduced the ratio of NAD＋ to NADPH in HKC cells,resulting in attenuated SIRT1 protein expression and enzymatic activity,thus suggesting the modulation of SIRT1 at the post-transcriptional levels.Conclusion NaDC3 promotes renal senescence by inhibition of NAD＋-dependent SIRT1.

关 键 词：能量代谢 NAD 肾脏衰老 SIRT1 NaDC3 

分 类 号：R692[医药卫生—泌尿科学]