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Nutrition. 2010 Nov-Dec;26(11-12):1146-50. doi: 10.1016/j.nut.2009.08.019. Epub 2010 Jan 15.

Hyperglycemia-induced endoplasmic reticulum stress in endothelial cells.

Author information

1
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida, Jacksonville, Florida, USA. mae.sheikh-ali@jax.ufl.edu

Abstract

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.

PMID:
20080028
DOI:
10.1016/j.nut.2009.08.019
[Indexed for MEDLINE]

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