hERG钾通道通过降低氧化应激改善肝细胞糖代谢  

Human ether-α-go-go related gene channels improves glucose metabolism via antioxidative stress in HepG2 cells

作　　者：卢晶[1,2] 沈涵 程呈 宋丽妮[1,2] 张怡尘 谢荣荣[1,2] 袁明霞 杨金奎 Lu Jing Sheng Han Cheng Cheng Song Lini Zhang Yichen Xie Rongrong Yuan Mingxia Yang Jinkui(Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China)

机构地区：[1]首都医科大学附属北京同仁医院内分泌科,北京100730 [2]糖尿病防治研究北京市重点实验室,北京100730

出　　处：《首都医科大学学报》2017年第2期156-160,共5页Journal of Capital Medical University

基　　金：国家自然科学基金(81370946;81400824;81300726);北京市自然科学基金(7131005);首都医科大学附属北京同仁医院科研基金(TRYY-KYJJ-2016-013)~~

摘　　要：目的研究hERG钾通道(human ether-α-go-go related gene channels)在肝细胞中与糖代谢的关系。方法用hERG钾通道过表达载体转染人类肝癌细胞系(liver hepatocellular carcinoma,HepG2)细胞,通过荧光定量PCR(real-time PCR,RTPCR)和蛋白印迹(Western blotting)法检测糖代谢、糖异生、氧化应激及还原型烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide 2'-phosphate,NADPH)相关亚基的表达。结果 hERG钾通道蛋白可在肝脏细胞中表达,将hERG钾通道过表达于HepG2细胞后,糖异生相关基因葡萄糖-6-磷酸激酶(glucose-6-phosphatase,G6Pase)表达显著降低,而磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase,PEPCK)表达有降低。胰岛素表达相关基因葡萄糖转运蛋白2(glucose transporter type 2,GLUT2)、胰岛素受体底物2(insulin receptor substrate,IRS-2)和腺苷酸活化蛋白激酶α亚基2[(adenosine 5’-monophosphate(AMP)-activated protein kinase),AMPKα2]的表达水平均显著增高。NADPH4种亚基p22、p47、p67和p91表达均显著降低。结论 hERG钾通道可以通过降低氧化应激改善肝细胞内糖代谢。Objective To evaluate the effect of the new pathway of human ether-α-go-go related gene （hERG） channels on glucose metabolism in hepatic cells.Methods Liver hepatocellular carcinoma （HepG2） cells were transfected with hERG channels over-expression plasmid DNA.pcDNA3.1-GFP plasmid was used as a negative control.The expression of hERG,phosphoenolpyruvate carboxykinase（PEPCK） and glucose-6-phosphatase （G6Pase） were detected by Western blotting.The mRNA level of glucose transporter type 2 （GLUT2）,insulin receptor substrate （IRS-2）,adenosine 5＇-monophosphate（AMP）-activated protein kinase （AMPKα2）,p22,p47,p67 and p91 were observed by real-time PCR（RT-PCR）.Results The experiments showed that hERG gene can be expressed in HepG2 cells.Over-expression of hERG gene in HepG2 cells could down-regulate the expression of PEPCK,G6Pase.while GLUT2,IRS-2,AMPKα2 genes were up-regulated.Over-expression of hERG gene also inhibited the relative mRNA level of p22,p47,p67and p91.Conclusion hERG channels could be involved in improving glucose metabolism via anti-oxidative effects.

关 键 词：人ether-α-go-go相关基因 胰岛素抵抗 氧化应激 糖代谢 

分 类 号：R587.1[医药卫生—内分泌]