vitamin-k-semiquinone-radical and 2-oxothiazolidine-4-carboxylic-acid

Using a prokaryote (Escherichia coli) and a metazoa-resembling eukaryote (Ochromonas danica), we surveyed antioxidants which might overcome redox stress imposed by menadione sodium bisulphite (MD) and buthionine sulphoximine (BSO). BSO oxidant stress was evident only in O. danica; MD oxidant stress was evident in both organisms. Glutathione, its precursors, e.g. cysteine, homocysteine, and 2-oxo-4-thiazolidine carboxylic acid, and red blood cells, emerged as prime antioxidants for relieving BSO and MD oxidant stress. BSO and MD oxidant activity and antioxidant-annulling effect in O. danica were judged comparable to those found in animal cells whereas the results E. coli were not entirely equivalent. The O. danica system emerged as a practical, rapid, and useful system for pinpointing oxidant stressors and antioxidants, and shows promise for studies with mammalian systems.

Topics: Antioxidants; Buthionine Sulfoximine; Cysteine; Escherichia coli; Eukaryota; Free Radicals; Glutathione; Homocysteine; Methionine Sulfoximine; Oxidative Stress; Pyrrolidonecarboxylic Acid; Thiazoles; Thiazolidines; Vitamin K; Vitamin K 3

Prostaglandin A2 (PGA2) stimulates the biosynthesis of gamma-glutamylcysteine synthetase and elevates glutathione (GSH) contents in cultured mammalian cells. To clarify the importance of gamma-glutamylcysteine synthetase induction in the defence of endothelial cells against oxidative stress, the effect of PGA2 on menadione (2-methyl-1,4-naphthoquinone)-induced cell injury was examined. Incubation of porcine aorta endothelial cells with menadione produced marked loss of cellular GSH and protein sulfhydryl groups, followed by leakage of lactic dehydrogenase (LDH) into the culture medium. The LDH leakage and modification of protein thiol was, however, completely prevented by pretreatment of the cells with PGA2. The protective effect of PGA2 was more potent than that of cysteine delivery agents such as methionine, N-acetylcysteine or 2-oxo-4-thiazolidine carboxylic acid (OTC). The results suggest that cellular GSH plays an important role in the defence against oxidative stress, and induction of gamma-glutamylcysteine synthetase is effective for protecting vascular endothelial cells.

Topics: Animals; Aorta; Cells, Cultured; Cysteine; Dose-Response Relationship, Drug; Endothelium, Vascular; Glutathione; Methionine; Prostaglandins A; Pyrrolidonecarboxylic Acid; Swine; Thiazoles; Thiazolidines; Time Factors; Vitamin K