Comparative toxicity of oxidatively modified low-density lipoprotein and lysophosphatidylcholine in cultured vascular endothelial cells.
Oxidative modification of low-density lipoprotein (LDL) may play an important role in the initiation and progression of atherosclerosis. We previously showed that the cytotoxicity of oxidized LDL (oxLDL) depended on the level of lipid hydroperoxides. Meanwhile, it has been shown that during LDL oxidation, a significant part of the LDL phosphatidylcholine (PC) is degraded to lysophosphatidylcholine (LPC) by an intrinsic phospholipase A2-like activity, and that LPC is toxic to various cells. In the present study, we compared the toxicity of oxLDL with that of LPC in cultured bovine aortic endothelial cells. Cytotoxicity induced by LPC, assessed by the release of lactate dehydrogenase (LDH), reached a plateau within 1 h. LDH release induced by oxLDL occurred much later, at about 3 h, and increased linearly until nearly all the LDH was released at 10 h. The addition of deferoxamine, a Fe3+ chelator, to the reaction medium prevented the toxic effects of oxLDL, but not of LPC. Native LDL and oxLDL inhibited the toxicity of LPC, while native LDL promoted the toxicity of oxLDL. Albumin inhibited the toxicity of LPC but not of oxLDL. Preincubation of endothelial cells with an antioxidant, probucol, protected against oxLDL toxicity, but not against LPC toxicity. These results suggest that lipid hydroperoxides associated with the oxLDL particle, not LPC, constitute the toxic moiety of oxLDL. These substances may generate lipid peroxyl and alkoxyl radicals in the presence of ionic iron, probably from intracellular iron stores in endothelial cells, and produce cytotoxicity.
Naito
M
M
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Yamada
K
K
Hayashi
T
T
Asai
K
K
Yoshimine
N
N
Iguchi
A
A
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000633:toxicity*; D008244:Lysophosphatidylcholines / Q000633:toxicity*; D016877:Oxidants
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D016877:Oxidants; D007770:L-Lactate Dehydrogenase