Oxidation of liposomal cholesterol and its effect on phospholipid peroxidation.
Lipid peroxidation is believed to play an important role in the pathogenesis of many diseases. Much research has therefore been devoted to peroxidation of different lipids in biomembranes and in model systems (liposomes) of different compositions. Yet, in spite of the relative simplicity of the liposomes, the existing literature is insufficient to reach definite conclusions regarding basic questions including the susceptibility of cholesterol to oxidation, its effect on the peroxidation of polyunsaturated phospholipids such as palmitoyllinoleoylphosphatidylcholine (PLPC) and how cholesterol influences the effect of water-soluble antioxidants such as urate on the peroxidation. The aim of the present study was to clarify these issues. Its major findings are that: (i) AAPH-induced peroxidation of cholesterol is slow and independent of the peroxidation of PLPC. In turn, AAPH-induced peroxidation of PLPC is not affected by cholesterol, independent of the presence of urate in the system. (ii) Cholesterol is not susceptible to copper-induced oxidation, but its inclusion in PLPC liposomes affects the peroxidation of PLPC, slowing down the initial stage of oxidation but promoting later stages. (iii) Addition of urate accelerates copper-induced peroxidation of PLPC in the absence of cholesterol, whereas in cholesterol-containing liposomes it inhibits PLPC oxidation. We attribute the complexity of the observed kinetics to the known cholesterol-induced rigidization of liquid crystalline bilayers.
Schnitzer
E
E
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel.
Pinchuk
I
I
Bor
A
A
Leikin-Frenkel
A
A
Lichtenberg
D
D
D000578:Amidines / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers; D015227:Lipid Peroxidation; D008081:Liposomes / Q000737:chemistry*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*
D000578:Amidines; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; C046728:2,2'-azobis(2-amidinopropane); D002784:Cholesterol