hERG钾通道通过降低氧化应激改善肝细胞糖代谢

doi:10.3969/j.issn.1006-7795.2017.02.003

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (2): 156-160.doi: 10.3969/j.issn.1006-7795.2017.02.003

hERG钾通道通过降低氧化应激改善肝细胞糖代谢

卢晶^1,2, 沈涵^1,2, 程呈^1,2, 宋丽妮^1,2, 张怡尘^1,2, 谢荣荣^1,2, 袁明霞^1,2, 杨金奎^1,2

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

收稿日期:2017-01-20 出版日期:2017-03-21 发布日期:2017-04-17
通讯作者: 杨金奎,E-mail:jinkui.yang@gmail.com E-mail:jinkui.yang@gmail.com
基金资助:
国家自然科学基金（81400824，81370946，81300726），北京市自然科学基金（7131005）

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

Lu Jing^1,2, Sheng Han^1,2, Cheng Cheng^1,2, Song Lini^1,2, Zhang Yichen^1,2, Xie Rongrong^1,2, Yuan Mingxia^1,2, Yang Jinkui^1,2

1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
2. Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China

Received:2017-01-20 Online:2017-03-21 Published:2017-04-17
Supported by:
This study was supported by National Natural Science Foundation of China (81400824, 81370946, 81300726), Natural Science Foundation of Beijing (7131005)

摘要/Abstract

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，RT-PCR）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。

关键词: 人ether-α-go-go相关基因, 胰岛素抵抗, 氧化应激, 糖代谢

Abstract: 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.

Key words: human ether-α-go-go related gene channels, insulin resistance, oxidative stress, glucose metabolism

中图分类号:

R587.1

卢晶, 沈涵, 程呈, 宋丽妮, 张怡尘, 谢荣荣, 袁明霞, 杨金奎. hERG钾通道通过降低氧化应激改善肝细胞糖代谢[J]. 首都医科大学学报, 2017, 38(2): 156-160.

Lu Jing, Sheng Han, Cheng Cheng, Song Lini, Zhang Yichen, Xie Rongrong, Yuan Mingxia, Yang Jinkui. Human ether-α-go-go related gene channels improves glucose metabolism via anti-oxidative stress in HepG2 cells[J]. Journal of Capital Medical University, 2017, 38(2): 156-160.

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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 anti-oxidative stress in HepG2 cells

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