title: Pb2+ promotes lipid oxidation and alterations in membrane physical properties.
abstract: Experimental evidence suggests that cellular damage mediated by oxidants could be involved in the pathology associated with lead (Pb) toxicity. We investigated the effect of Pb2+ on lipid oxidation in liposomes using different initiators. In the presence of Fe2+, Pb2+ (12.5-200 microM) stimulated lipid oxidation in phosphatidylcholine:phosphatidylserine-containing liposomes, measured as 2-thiobarbituric acid-reactive substances (TBARS) and conjugated dienes. This stimulatory effect depended on the presence of membrane negative charges and on bilayer integrity. Pb2+ did not stimulate TBARS formation in the presence of 25 mM 2,2'-azo-bis (2,4 dimethylvaleronitrile (AMVN) and 2,2' azobis (2-amidinopropane) (AAPH). Pb2+ significantly stimulated TBARS production and NADH oxidation in the presence of photoactivated rose Bengal. The use of specific inhibitors indicated that several reactive oxygen species were involved in the pro-oxidant action of Pb2+. Pb2+ (12.5-200 microM) caused membrane lateral phase separation and this effect was positively correlated with its capacity to stimulate Fe2+ and rose Bengal-initiated TBARS production. Pb2+ could bind to the membrane and act to stimulate lipid oxidation by causing changes in membrane physical properties. Through this mechanism Pb2+ would favor the propagation of lipid oxidation. By causing lateral phase separation and/or by increasing lipid oxidation rates, Pb2+ could be cytotoxic by altering membrane-related processes.
authors: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Argentina.
authors: V N
authors: VN
authors: Adonaylo
authors: P I
authors: PI
authors: Oteiza
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D002417:Cattle; D005609:Free Radicals; D007501:Iron / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes / Q000737:chemistry / Q000187:drug effects*; D008561:Membrane Fusion; D009243:NAD / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D012395:Rose Bengal / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000578:Amidines; D001391:Azo Compounds; D005609:Free Radicals; D008051:Lipid Bilayers; D008081:Liposomes; D009570:Nitriles; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D017392:Thiobarbituric Acid Reactive Substances; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D009243:NAD; D012395:Rose Bengal; D007854:Lead; C046728:2,2'-azobis(2-amidinopropane); D007501:Iron