Potentiation of free radical-induced lipid peroxidative injury to sarcolemmal membranes by lipid amphiphiles.
The effects of naturally occurring lipid amphiphiles on free radical-mediated peroxidative injury in isolated canine sarcolemma were studied. Highly enriched canine myocytic sarcolemmal membranes were preincubated for 10 min at 37 degrees C with or without different amphiphilic lipids before the addition of a free radical-generating system consisting of dihydroxyfumarate and Fe3+-ADP. Lipid peroxidation, assayed as malondialdehyde formation, was catalyzed linearly up to 40 min in the control samples. Pretreatment of the sarcolemma with palmitoyl-CoA, palmitoylcarnitine, or lysophosphatidylcholine accelerated the initial rates (20 min) of peroxidation in a concentration-dependent manner (10-100 microM) and achieved maximal stimulation (240%, 160%, and 210%, respectively, of controls) at 50 microM concentrations of each of these amphiphiles. However, free fatty acids, CoA, and carnitine were without effect. These promoting effects of the amphiphiles persisted over a wide pH range (pH 6.0-7.8) and exhibited additive effects when lower levels of different amphiphiles were combined together. Associated with the accelerated rates of peroxidation produced by palmitoyl-CoA and palmitoylcarnitine were greater losses in the activity of sarcolemmal (Na,K)-ATPase. Since all three kinds of amphiphilic lipids accumulate during ischemia, this study suggests a novel mechanism of potentiation of sacolemmal membrane injury when free radicals are present.
D000818:Animals; D004285:Dogs; D005609:Free Radicals; D005650:Fumarates / Q000494:pharmacology; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D010084:Oxidation-Reduction; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D010172:Palmitoylcarnitine / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D005609:Free Radicals; D005650:Fumarates; D008054:Lipid Peroxides; C005998:dihydroxyfumarate; D010171:Palmitoyl Coenzyme A; D010172:Palmitoylcarnitine; D000254:Sodium-Potassium-Exchanging ATPase