Hyperglycemia-induced endoplasmic reticulum stress in endothelial cells

详细信息    查看全文

• 作者：Mae Sheikh-Ali ; Senan Sultan ; Abdul-Razzak Alamir ; Michael J. Haas ; Arshag D. Mooradian
• 关键词：Endoplasmic reticulum ; Oxidative stress ; Hyperglycemia ; Mitochondria
• 刊名：Nutrition
• 出版年：2010
• 出版时间：November-December 2010
• 年：2010
• 卷：26
• 期：11-12
• 页码：1146-1150
• 全文大小：228 K

文摘

Objective

Hyperglycemia-induced endothelial cell dysfunction in vascular disease can occur due to increased oxidative stress and a concomitant increase in endoplasmic reticulum (ER) stress. To investigate whether these cellular stresses are independent or causally linked, we determined whether or not specific glycolytic intermediates that induce oxidative stress also induce ER stress.

Methods

Human umbilical vein endothelial cells were treated with dextrose, partially metabolizable (e.g., fructose and galactose) and non-metabolizable sugars (e.g., 3-O-methyglucose), and various intermediates of the glycolytic and tricarboxylic acid pathways. Activation of the unfolded protein response and subsequent generation of ER stress was measured by the ER stress-responsive alkaline phosphatase method, and superoxide (SO) generation was measured using the hydro-ethidene–fluorescence method. The mitochondrial origin of the SO and the generation of ER stress by dextrose and the intermediate metabolites were confirmed with experiments using allopurinol and diphenyleneiodonium chloride to block SO generation by xanthine oxidase and nicotinamide adenosine dinucleotide phosphate oxidase, respectively.

Results

Although ER stress could be induced by glycolytic intermediates up to and including pyruvate, the SO generation occurred in the presence of glycolytic and mitochondrial metabolites.

Conclusion

Although the mitochondria are the site of signals generated by dextrose to initiate oxidative stress, the dextrose-induced ER stress, unlike SO generation, does not require pyruvate oxidation in the mitochondria.