Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells.
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 Q10 in diabetes with hypertension, the direct effect of coenzyme Q10 on the endothelial functions has not been examined. In the present study, we therefore investigated the protective effect of coenzyme Q10 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 Cbeta2, and increase in endothelial nitric oxide synthase expression. Treatment with coenzyme Q10 strongly inhibited these changes in HUVEC under high glucose condition. In addition, coenzyme Q10 inhibited high glucose-induced cleavage of poly(ADP-ribose) polymerase, an endogenous caspase-3 substrate. These results suggest that coenzyme Q10 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 Q10 displayed potent inhibitory effects against these endothelial abnormalities. Thus, we provide the first evidence that coenzyme Q10 has a beneficial effect in protecting against the endothelial dysfunction by high glucose-induced oxidative stress in vitro.
Tsuneki
Hiroshi
H
Department of Clinical Pharmacology, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. htsuneki@pha.u-toyama.ac.jp
Sekizaki
Naoto
N
Suzuki
Takashi
T
Kobayashi
Shinjiro
S
Wada
Tsutomu
T
Okamoto
Tadashi
T
Kimura
Ikuko
I
Sasaoka
Toshiyasu
T
D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003067:Coenzymes / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology
D003067:Coenzymes; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D014815:Vitamins; D018799:Intercellular Adhesion Molecule-1; D014451:Ubiquinone; D052250:Nitric Oxide Synthase Type III; D011493:Protein Kinase C; C024989:coenzyme Q10; D005947:Glucose