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晚期糖基化终产物对人脐静脉内皮细胞葡萄糖-6-磷酸脱氢酶的影响

何美华^*, 张艳

北京大学医学部人体解剖与组织胚胎学系，北京 100191

摘要

糖尿病和长期高血糖会导致血管内皮上晚期糖基化终产物的形成。晚期糖基化终产物在血管内皮上的聚集则进一步引起氧化应激和血管的损伤。而葡萄糖-6-磷酸脱氢酶是机体内NADPH的主要来源之一，对于维持机体内的氧化还原平衡非常重要。葡萄糖-6-磷酸脱氢酶活性不足会导致血管内皮细胞氧化应激。本研究的主要目的是研究晚期糖基化终产物对人脐静脉内皮细胞内葡萄糖-6-磷酸脱氢酶活性和表达的影响。结果显示，晚期糖基化终产物修饰的牛血清白蛋白(AGE-BSA, 100 µg/mL)孵育24 h可以显著提高人脐静脉内皮细胞内自由基的量[(48.89 ± 5.28)%]，同时显著降低葡萄糖-6-磷酸脱氢酶的活性[(61.25 ± 11.2)%]。而AGE-BSA孵育8 h可降低葡萄糖-6-磷酸脱氢酶mRNA的表达[(27.92 ± 6.73)%]，AGE-BSA孵育24 h则可降低葡萄糖-6-磷酸脱氢酶蛋白的表达[(23.72 ± 2.44)%]。这些结果说明，晚期糖基化终产物会导致人脐静脉内皮细胞内氧化应激增加，同时导致内皮细胞内葡萄糖-6-磷酸脱氢酶活性降低、蛋白表达下降。

关键词： 晚期糖基化终产物; 葡萄糖-6-磷酸脱氢酶; 氧化应激; 人脐静脉内皮细胞

Advanced glycation end products inhibit glucose-6-phosphate dehydrogenase activity and expression in human umbilical vein endothelial cells

HE MeiHua^*, ZHANG Yan

Department of Anatomy, Peking University Health Science Center, Beijing 100191, China

Abstract

Increased formation of advanced glycation end-products (AGEs) is occurred in hyperglyceamia and diabetes, leading to oxidative stress and progression of diabetic vascular diseases. Glucose-6-phosphate dehydrogenase (G6PD), the principal source of NADPH, serves as an antioxidant enzyme to modulate the redox milieu. Deficiency of G6PD activity is associated with increased endothelial cell oxidative stress. Current study is designed to investigate the effects of AGEs on G6PD activity and expression in human umbilical vein endothelial cells. Treatment of AGE-modified bovine serum albumin (AGE-BSA, 100 µg/mL, 24 h), but not native BSA, to human umbilical vein endothelial cells increased ROS generation by (48.89 ± 5.28)%. G6PD activity was decreased by AGE-BSA treatment by (61.25 ± 11.2)%. The expression of G6PD at mRNA and protein levels was also decreased by AGE-BSA treatment by (27.92 ± 6.73)% and (23.72 ± 2.44)%, respectively. These results suggest that AGEs could result in G6PD deficiency in human umbilical vein endothelial cells by inhibiting the expression of G6PD at mRNA and protein levels and G6PD activity.

Key words: advanced glycation end products; glucose-6-phosphate dehydrogenase; oxidative stress; human umbilical vein endothelial cells

收稿日期：2012-03-13　　录用日期：2012-08-09

通讯作者：何美华　　E-mail: hemeihua@bjmu.edu.cn

引用本文：

何美华, 张艳. 晚期糖基化终产物对人脐静脉内皮细胞葡萄糖-6-磷酸脱氢酶的影响[J]. 生理学报 2012; 64 (6): 646-650.

HE MeiHua, ZHANG Yan. Advanced glycation end products inhibit glucose-6-phosphate dehydrogenase activity and expression in human umbilical vein endothelial cells. Acta Physiol Sin 2012; 64 (6): 646-650 (in Chinese with English abstract).