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 dieta ry Al3+ on myelin lipid composition and lipid oxidation. We found: (1) a significantly higher (104%; P < 0.01) content of brain myelin galac tolipids in the high-Al3+ group than in controls, and, (2) a significa nt correlation (r(2) = 0.70; P < 0.01) between the concentration of my elin galactolipids and TEARS (2-thiobarbituric acid-reactive substance s) content, a parameter of lipid oxidation. Based on these results, we evaluated in an in vitro model (liposomes) whether galactolipids coul d affect the capacity of Al3+ to stimulate Fe2+-initiated lipid oxidat ion, and whether this effect could be due to the promotion of changes in membrane physical properties (membrane phase separation and rigidif ication). The presence of galactolipids (10-40 mol%) in the liposomes caused a concentration-dependent increase in the stimulatory effect of Al3+ On Fe2+-induced TEARS production, and on the ability of Al3+ to induce phase separation and membrane rigidification. The capacity of A l3+ (10-100 mu M) to induce lateral phase separation in liposomes comp osed of hosphatidylcholine/phosphatidylserine/galactolipid (36 : 24 : 40, molar ratio) was correlated significantly (r(2) = 0.99; P < 0.001) with the stimulatory action of Al3+ on Fe2+-induced TEARS production. We propose that the high content of galactolipids found in myelin fro m Al3+-intoxicated mice could favour Al3+-induced changes in membrane physical properties, with the subsequent acceleration of lipid oxidati on rates.