Verstraeten S V, Keen C L, Golub M S, Oteiza P I
Department of Biological Chemistry-IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
Biochem J. 1998 Aug 1;333 ( Pt 3)(Pt 3):833-8. doi: 10.1042/bj3330833.
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.
在本研究的第一部分中，我们调查了孕期及出生后早期小鼠暴露于高剂量膳食铝离子（Al³⁺）对髓磷脂脂质组成及脂质氧化的影响。我们发现：（1）高铝组小鼠脑髓磷脂半乳糖脂含量显著高于对照组（高104%；P<0.01）；（2）髓磷脂半乳糖脂浓度与脂质氧化参数硫代巴比妥酸反应性物质（TBARS）含量之间存在显著相关性（r²=0.70；P<0.01）。基于这些结果，我们在体外模型（脂质体）中评估了半乳糖脂是否会影响Al³⁺刺激亚铁离子引发脂质氧化的能力，以及这种影响是否归因于促进膜物理性质的改变（膜相分离和僵化）。脂质体中半乳糖脂（10 - 40摩尔%）的存在导致Al³⁺对亚铁离子诱导的TBARS生成以及对Al³⁺诱导相分离和膜僵化能力的刺激作用呈浓度依赖性增加。Al³⁺（10 - 100微摩尔）在由磷脂酰胆碱/磷脂酰丝氨酸/半乳糖脂（摩尔比36:24:40）组成的脂质体中诱导横向相分离的能力与Al³⁺对亚铁离子诱导的TBARS生成的刺激作用显著相关（r²=0.99；P<0.001）。我们提出，在铝中毒小鼠的髓磷脂中发现的高含量半乳糖脂可能有利于铝离子诱导的膜物理性质改变，进而加速脂质氧化速率。
