5-aminolevulinic acid induces lipid peroxidation in cardiolipin-rich liposomes.
5-Aminolevulinic acid (ALA), a heme precursor accumulated in lead poisoning and acute intermittent porphyria, is known to undergo metal-catalyzed aerobic oxidation to yield reactive oxygen species. In phosphatidylcholine:cardiolipin (80:20) liposomes ALA (0.1-3.0 mM) promoted lipid peroxidation as evaluated by the formation of conjugated dienes and 2-thiobarbituric-reactive substances (TBARS). TBARS formation was dependent on ALA concentration and incubation time. ALA-induced lipid peroxidation was associated with an increase in liposome permeability as measured by the release of encapsulated carboxyfluorescein. alpha-Tocopherol (0.1-0.5 mol %), an efficient oxyradical scavenger, inhibits lipid peroxidation and prevents carboxyfluorescein release, suggesting that the permeabilization of liposomes is mainly due to lipid peroxidation. Cardiolipin, a major component of mitochondrial inner membrane, was particularly susceptible to ALA-induced lipid peroxidation. These results may be relevant to the previously observed Ca(2+)-dependent permeabilization of the inner membrane of rat liver mitochondria promoted by external 0.1-1.0 mM ALA; this mechanism has been implicated in the pathophysiology of acute intermittent porphyria and lead poisoning.
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
P I
PI
Oteiza
E J
EJ
Bechara
D000622:Aminolevulinic Acid / Q000737:chemistry*; D002308:Cardiolipins / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008081:Liposomes; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D014810:Vitamin E / Q000494:pharmacology
D002308:Cardiolipins; D005227:Fatty Acids; D008054:Lipid Peroxides; D008081:Liposomes; D010713:Phosphatidylcholines; D014810:Vitamin E; D000622:Aminolevulinic Acid