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Membrane composition can influence the rate of Al3+-mediated lipid oxidation: effect of galactolipids.

ABSTRACT: 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.

SUBMITTER: Verstraeten SV

PROVIDER: S-EPMC1219651 | biostudies-other | 1998 Aug

REPOSITORIES: biostudies-other

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Project description:Some lipid mixtures form membranes containing submicroscopic (nanodomain) ordered lipid domains (rafts). Some of these nanodomains are so small (radius <5 nm) that they cannot be readily detected with Förster resonance energy transfer (FRET)-labeled lipid pairs with large Ro. We define such domains as ultrananodomains. We studied the effect of lipid structure/composition on the formation of ultrananodomains in lipid vesicles using a dual-FRET-pair approach in which only one FRET pair had Ro values that were sufficiently small to detect the ultrananodomains. Using this approach, we measured the temperature dependence of domain and ultrananodomain formation for vesicles composed of various mixtures containing a high-Tm lipid (brain sphingomyelin (SM)) or dipalmitoyl phosphatidylcholine (DPPC)), low-Tm lipid (dioleoylphosphatidylcholine (DOPC) or 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC)), and a lower (28 mol %) or higher (38 mol %) cholesterol concentration. For every lipid combination tested, the thermal stabilities of the ordered domains were similar, in agreement with our prior studies. However, the range of temperatures over which ultrananodomains formed was highly lipid-type dependent. Overall, vesicles that were closest to mammalian plasma membrane in lipid composition (i.e., with brain SM, POPC, and/or higher cholesterol) formed ultrananodomains in preference to larger domains over the widest temperature range. Relative to DPPC, the favorable effect of SM on ultrananodomain formation versus larger domains was especially large. In addition, the favorable effect of a high cholesterol concentration, and of POPC versus DOPC, on the formation of ultrananodomains versus larger domains was greater in vesicles containing SM than in those containing DPPC. We speculate that it is likely that natural mammalian lipids are tuned to maximize the tendency to form ultrananodomains relative to larger domains. The observation that domain size is more sensitive than domain formation to membrane composition has implications for how membrane domain properties may be regulated in vivo.

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Membrane composition can influence the rate of Al3+-mediated lipid oxidation: effect of galactolipids.

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