IMPLICATION OF DICARBOXYLIC PHOSPHOLIPIDS IN THE DELETERIOUS EFFECTS INDUCED BY FREE-RADICALS

Peroxidation of low-density lipoproteins (LDLs), induced by copper ion s, was followed by the formation of phosphatidylcholines having a dica rboxylic acid in the 2-position of the glycerol moiety. In the present study, we examined the calcium ionophore activity and the ''cytotoxic '' effect of these phospholipids. Added at micromolar concentrations t o preformed multilamellar liposomes, they provoked calcium influx. It was also observed that calcium influx into multilamellar liposomes con taining dicarboxylic phospholipids was dependent on the mole percent o f dicarboxylic agent and that influx was more pronounced than with pho sphatidic acid preincorporated in the liposomes. The cytotoxic effect was examined in cultured bovine endothelial cells and human fibroblast s. Dicarboxylic phospholipids were found to be highly cytotoxic and th e effect increased with the concentration of the agent in the culture medium. Since the dicarboxylic phospholipid content of LDLox correlate d with the amount of dicarboxylic phospholipid necessary to cause deat h of culture cells, our data support the hypothesis that these phospho lipids may be responsible for the toxic effect exerted by oxidized LDL s. These findings show that dicarboxylic phospholipids also can be res ponsible for the toxic effect exerted by peroxidized LDLs.