Ascorbic acid blunts oxidant stress due to menadione in endothelial cells.
Endothelial cells are exposed to potentially damaging reactive oxygen species generated both within the cells and in the bloodstream and underlying vessel wall. In this work, we studied the ability of ascorbic acid to protect cultured human-derived endothelial cells (EA.hy926) from oxidant stress generated by the redox cycling agent menadione. Menadione caused intracellular oxidation of dihydrofluorescein, which required the presence of D-glucose in the incubation medium, and was inhibited by intracellular ascorbate and desferrioxamine. At concentrations of 100 microM and higher, menadione depleted the cells of both GSH and ascorbate, and ascorbate loading partially prevented the decrease in GSH due to menadione. Menadione increased L-arginine uptake by the cells, but inhibited endothelial nitric oxide synthase, an effect that was prevented by acute loading with ascorbate. Ascorbate blunts menadione-induced oxidant stress in EA.hy926 cells, which may help to preserve nitric oxide synthase activity under conditions of excessive oxidant stress.
May
James M
JM
Department of Medicine, Vanderbilt University School of Medicine, 715 Preston Research Building, Nashville, TN 37232-6303, USA. james.may@vanderbilt.edu
Qu
Zhi-chao
ZC
Li
Xia
X
D001205:Ascorbic Acid / Q000494:pharmacology*; D001692:Biological Transport; D002460:Cell Line; D002478:Cells, Cultured; D003683:Dehydroascorbic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005456:Fluorescent Dyes; D006801:Humans; D007700:Kinetics; D018384:Oxidative Stress / Q000187:drug effects*; D024483:Vitamin K 3 / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D005456:Fluorescent Dyes; D024483:Vitamin K 3; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid