Membrane composition can influence the rate of Al3+-mediated lipid oxidation: effect of galactolipids.
In the first part of the present study we investigated the effects of pre-natal and early postnatal exposure of mice to high levels of dietary Al3+ on myelin lipid composition and lipid oxidation. We found: (1) a significantly higher (104%; P<0.01) content of brain myelin galactolipids in the high-Al3+ group than in controls, and, (2) a significant correlation (r2=0.70; P<0.01) between the concentration of myelin galactolipids and TBARS (2-thiobarbituric acid-reactive substances) content, a parameter of lipid oxidation. Based on these results, we evaluated in an in vitro model (liposomes) whether galactolipids could affect the capacity of Al3+ to stimulate Fe2+-initiated lipid oxidation, and whether this effect could be due to the promotion of changes in membrane physical properties (membrane phase separation and rigidification). The presence of galactolipids (10-40 mol%) in the liposomes caused a concentration-dependent increase in the stimulatory effect of Al3+ on Fe2+-induced TBARS production, and on the ability of Al3+ to induce phase separation and membrane rigidification. The capacity of Al3+ (10-100 microM) to induce lateral phase separation in liposomes composed of phosphatidylcholine/phosphatidylserine/galactolipid (36:24:40, molar ratio) was correlated significantly (r2=0.99; P<0. 001) with the stimulatory action of Al3+ on Fe2+-induced TBARS production. We propose that the high content of galactolipids found in myelin from Al3+-intoxicated mice could favour Al3+-induced changes in membrane physical properties, with the subsequent acceleration of lipid oxidation rates.
Department of Biological Chemistry-IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
S V
SV
Verstraeten
C L
CL
Keen
M S
MS
Golub
P I
PI
Oteiza
D000535:Aluminum / Q000506:poisoning / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D004032:Diet; D005260:Female; D005454:Fluorescence Polarization; D038983:Galactolipids; D005690:Galactose / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D038983:Galactolipids; D006017:Glycolipids; D008563:Membrane Lipids; D017392:Thiobarbituric Acid Reactive Substances; D000535:Aluminum; D005690:Galactose