LDL oxidized with iron in the presence of homocysteine/cystine at acidic pH has low cytotoxicity despite high lipid peroxidation.
Fe(III) can have a strong oxidizing effect in the presence of reductants at acidic pH, which may occur under anaerobic conditions or in regions of inflammation. Low density lipoprotein (LDL) oxidation with Fe(III) and homocysteine/cystine at acidic pH provoked mainly formation of lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS) in the absence of significant protein modification. Even when oxidized to a high TBARS content, LDL oxidized at acidic pH was not cytotoxic when added to THP-1 monocytes in a concentration causing cell death when LDL was oxidized to a similar TBARS content at plasma pH with Fe(III) or Cu(II) in the presence or absence of homocysteine/cystine. Inducible nitric oxide production by RAW264.7 mouse macrophages was only weakly inhibited by LDL oxidized at acidic pH, even if acetylated before oxidation to increase uptake, as compared to LDL oxidized with Cu(II) at plasma pH to a similar TBARS content or anodic electrophoretic mobility. LDL oxidized at acidic pH may mainly induce protective mechanisms against oxidative stress while causing little acute damage of cells.
Pfanzagl
Beatrix
B
Institute of Physiology, Center of Physiology and Pathophysiology, Medical University Vienna, Wien, Austria. beatrix.pfanzagl@meduniwien.ac.at
D000107:Acetylation / Q000187:drug effects; D000143:Acids / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D003553:Cystine / Q000378:metabolism* / Q000494:pharmacology; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000143:Acids; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D006710:Homocysteine; D009569:Nitric Oxide; D003553:Cystine; D003300:Copper; D007501:Iron