【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。更多还原

【Abstract】 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.更多还原