Protective role of intracellular glutathione against oxidized low density lipoprotein in cultured endothelial cells

• Published in: Biochemical and Biophysical Research Communications Vol. 163; no. 3; pp. 1466 - 1472
• Main Authors: Kuzuya, Masafumi, Naito, Michitaka, Funaki, Chiaki, Hayashi, Toshio, Asai, Kanichi, Kuzuya, Fumio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.09.1989; Elsevier BV
• Subjects: Animals; Antimetabolites; Antimetabolites - pharmacology; Aorta, Thoracic; Buthionine Sulfoximine; Cattle; Cell Survival; Cell Survival - drug effects; Cells, Cultured; Endothelium, Vascular; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Fetus; Glutathione; Glutathione - physiology; Kinetics; lipoprotein (low density); Lipoproteins, LDL; Lipoproteins, LDL - pharmacology; Methionine Sulfoximine; Methionine Sulfoximine - analogs & derivatives; Methionine Sulfoximine - pharmacology; Pyrrolidonecarboxylic Acid; Thiazoles; Thiazoles - pharmacology; Thiazolidines; NADPH; L-2-oxothiazolidine-4-caboxylate; low density lipoprotein; reduced nicotinamide adenine dinucleotide phosphate; glutathione; oxidized low density lipoprotein; MDA; OX-LDL; Dulbecco's phosphate-buffered saline; LDH; LDL; 5,5′-dithiobis(2-nitrobenzoic acid); malondialdehyde; GSH; DME; BSO; PBS; DTNB; lactate dehydrogenase; TBARS; thiobarbituric acid reacting substances; Dulbecco's modified Eagle's medium; CS; bovine calf serum; MEM; DL-buthionine-S,R-sulfoximine; OTC; phenol red free Eagle's minimum essential medium
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(89)91144-3

We examined the role of intracellular glutathione (GSH) in the defense of endothelial cells against oxidized low density lipoprotein (OX-LDL). Incubation of cultured bovine endothelial cells with OX-LDL produced a loss of intracellular GSH, followed by lysis. A decrease in the cellular stores of GSH by treating the endothelial cells with buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, increased the susceptibility of endothelial cells to lysis by OX-LDL. In contrast, an increase in cellular GSH level by treatment with L-2-oxothiazolidine-4-caboxylate, an effective intracellular cysteine delivery agent, reduced the toxicity of OX-LDL. These findings suggest that intracellular GSH plays an important role in the defense of endothelial cells against OX-LDL, and that the mechanism of OX-LDL toxicity is related to the depletion of intracellular GSH.