Nitric oxide donor compounds inhibit the toxicity of oxidized low-density lipoprotein to endothelial cells.
Photo-oxidized low-density lipoprotein is cytotoxic to bovine aortic endothelial cells in a concentration-dependent manner. Total cell killing occurs at a concentration of 600 mumol/l lipid hydroperoxide (LOOH). Selenium deficiency enhances the toxicity of LOOH such that 300 mumol/l LOOH is cytotoxic. This toxicity is inhibited by desferrioxamine, a transition metal ion chelator, and by butylatedhydroxytoluene, a potent inhibitor of lipid peroxidation. Toxicity is also inhibited by the nitric oxide donors S-nitrosoglutathione and spermine NONOate but not by reduced or oxidized glutathione and spermine. We propose that nitric oxide, released from these compounds, is inhibiting the toxicity of LOOH to selenium-deficient endothelial cells. Furthermore we hypothesize that the mechanism for this inhibition of toxicity is the scavenging of the propagatory peroxyl and alkoxyl free radicals, by nitric oxide, that are generated during peroxidation of cell membranes.
Struck
A T
AT
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226.
Hogg
N
N
Thomas
J P
JP
Kalyanaraman
B
B
D000818:Animals; D001013:Aorta, Thoracic; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D019803:Glutathione Disulfide; D007700:Kinetics; D008054:Lipid Peroxides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D026422:S-Nitrosoglutathione; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology*
D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D002084:Butylated Hydroxytoluene; D013096:Spermine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005978:Glutathione; D012643:Selenium; D003676:Deferoxamine; D019803:Glutathione Disulfide