Coenzyme Q 10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells

Abstract

Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of vascular complications in diabetes. Although some clinical evidences suggest the use of an antioxidant reagent coenzyme Q 10 in diabetes with hypertension, the direct effect of coenzyme Q 10 on the endothelial functions has not been examined. In the present study, we therefore investigated the protective effect of coenzyme Q 10 against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVEC). HUVEC exposed to high glucose (30 mM) exhibited abnormal properties, including the morphological and biochemical features of apoptosis, overproduction of reactive oxygen species, activation of protein kinase Cβ2, and increase in endothelial nitric oxide synthase expression. Treatment with coenzyme Q 10 strongly inhibited these changes in HUVEC under high glucose condition. In addition, coenzyme Q 10 inhibited high glucose-induced cleavage of poly(ADP-ribose) polymerase, an endogenous caspase-3 substrate. These results suggest that coenzyme Q 10 prevents reactive oxygen species-induced apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway. Moreover, consistent with previous reports, high glucose caused upregulation of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in HUVEC, and promoted the adhesion of U937 monocytic cells. Coenzyme Q 10 displayed potent inhibitory effects against these endothelial abnormalities. Thus, we provide the first evidence that coenzyme Q 10 has a beneficial effect in protecting against the endothelial dysfunction by high glucose-induced oxidative stress in vitro.