Oxidative stress effect on the integrity of lipid bilayers is modulated by cholesterol level of bilayers.
Large unilamellar vesicles (120-160 nm) composed of egg phosphatidylcholine (egg PC) containing approximately 22 wt% of polyunsaturated fatty acids (PUFA) and various mol% (0, 10, 22, or 45) of cholesterol were exposed to oxidative stress. The hydrophilic azo compound 2,2'-azobis-(2-amidinopropane)2HCl (AAPH) which was thermally decomposed to produce a constant flux of peroxy radicals was the source of the oxidative stress (< or = 48 h incubation at 37 degrees C). Cholesterol loss following the oxidation was up to 33%, while PUFA were more extensively damaged; loss was up to 52, 88, and 100% for C-18:2, C-20:4, and C-22:6, respectively. (ii) Oxidizability of cholesterol when quantified in absolute amount was three-fold higher when its level was 45 mol%. The interrelationship between bilayer structure, especially its lateral organization and free volume, and lipid peroxidation are discussed. Differential scanning calorimetry of oxidized multilamellar vesicles lacking cholesterol revealed that a high level of oxidative damage to egg phosphatidylcholine PUFA resulted in the loss of the gel to liquid-crystalline phase transition of egg PC (broad peak at around -8 degrees C).
Tirosh
O
O
Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Kohen
R
R
Katzhendler
J
J
Alon
A
A
Barenholz
Y
Y
D000578:Amidines / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005782:Gels; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010545:Peroxides / Q000378:metabolism / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D013696:Temperature
D000578:Amidines; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D005782:Gels; D008051:Lipid Bilayers; D008081:Liposomes; D010545:Peroxides; D010713:Phosphatidylcholines; C049375:perhydroxyl radical; C046728:2,2'-azobis(2-amidinopropane); D002784:Cholesterol