Korean Diabetes J.  2009 Apr;33(2):94-104. 10.4093/kdj.2009.33.2.94.

High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils

Affiliations
  • 1Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea. sonsm@pusan.ac.kr
  • 2Diabetes Center, Pusan National University Yangsan Hospital, Yangsan, Korea.

Abstract

BACKGROUND
Oxidative stress and inflammation are important factors in the pathogenesis of diabetes and contribute to the development of diabetic complications. To understand the mechanisms that cause vascular complications in diabetes, we examined the effects of high glucose and/or free fatty acids on the production of superoxide from neutrophils and their role in endothelial cell damage. METHODS: Human neutrophils were incubated in the media containing 5.5 mM D-glucose, 30 mM D-glucose, 3 nM oleic acid, or 30 microM oleic acid for 1 hour to evaluate superoxide production through NAD(P)H oxidase activation. Human aortic endothelial cells were co-cultured with neutrophils exposed to high glucose and oleic acid. We then measured neutrophil adhesion to endothelial cells, neutrophil activation and superoxide production, neutrophil-mediated endothelial cell cytotoxicity and subunits of neutrophil NAD(P)H oxidase. RESULTS: After 1 hour of incubation with various concentrations of glucose and oleic acid, neutrophil adherence to high glucose and oleic acid-treated endothelial cells was significantly increased compared with adhesion to low glucose and oleic acid-treated endothelial cells. Incubation of neutrophils with glucose and free fatty acids increased superoxide production in a dose-dependent manner. High glucose and oleic acid treatment significantly increased expression of the membrane components of NAD(P)H oxidase of neutrophil (gp91(phox)). Endothelial cells co-cultured with neutrophils exposed to high glucose and oleic acid showed increased cytolysis, which could be prevented by an antioxidant, N-acetylcysteine. CONCLUSION: These results suggest that high glucose and/orfree fatty acidsincrease injury of endothelial cells via stimulating NAD(P)H oxidase-induced superoxide production from neutrophils.

Keyword

Endothelial cells; NAD(P)H oxidase; Neutrophil; Oxidative stress

MeSH Terms

Acetylcysteine
Diabetes Complications
Endothelial Cells
Fatty Acids, Nonesterified
Glucose
Humans
Inflammation
Membranes
NADPH Oxidase
Neutrophil Activation
Neutrophils
Oleic Acid
Oxidative Stress
Superoxides
Acetylcysteine
Fatty Acids, Nonesterified
Glucose
NADPH Oxidase
Oleic Acid
Superoxides
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