Pamplona R, Portero-Otín M, Riba D, Requena J R, Thorpe S R, López-Torres M, Barja G
Department of Basic Medical Science, University of Lleida, Spain.
J Gerontol A Biol Sci Med Sci. 2000 Jun;55(6):B286-91. doi: 10.1093/gerona/55.6.b286.
Carbonyl compounds generated by the nonenzymatic oxidation of polyunsaturated fatty acids react with nucleophilic groups in proteins, leading to their modification. It has not been tested whether fatty acid unsaturation is related to steady-state levels of lipoxidation-derived protein modification in vivo. A low fatty acid unsaturation, hence a low protein lipoxidation, in tissues of longevous animals would be consistent with the free radical theory of aging, because membrane lipids increase their sensitivity to oxidative damage as a function of their degree of unsaturation. To evaluate the relationship between fatty acid composition, protein lipoxidation, and maximum life span (MLSP), we analyzed liver fatty acids and proteins from seven mammalian species, ranging in MLSP from 3.5 to 46 years. The results show that the peroxidizability index of fatty acids and the sensitivity to in vitro lipid peroxidation are negatively correlated with the MLSP. Based on gas chromatography and mass spectroscopy analyses, liver proteins of all these species contain malondialdehyde-lysine and Nepsilon-carboxymethyllysine adducts, two biomarkers of protein lipoxidation. The steady-state levels of malondialdehyde-lysine and Nepsilon-carboxymethyl lysine are directly related to the peroxidizability index and inversely related to the MLSP. We propose that a low degree of fatty acid unsaturation may have been selected in longevous mammals to protect their tissue lipids and proteins against oxidative damage while maintaining an appropriate environment for membrane function.
多不饱和脂肪酸非酶促氧化产生的羰基化合物与蛋白质中的亲核基团发生反应，导致蛋白质发生修饰。脂肪酸不饱和度是否与体内脂氧化衍生的蛋白质修饰稳态水平相关尚未得到验证。长寿动物组织中脂肪酸不饱和度低，因此蛋白质脂氧化程度低，这与衰老的自由基理论一致，因为膜脂对氧化损伤的敏感性随其不饱和度增加而增加。为了评估脂肪酸组成、蛋白质脂氧化和最大寿命（MLSP）之间的关系，我们分析了7种哺乳动物的肝脏脂肪酸和蛋白质，其MLSP范围为3.5至46年。结果表明，脂肪酸的过氧化指数和对体外脂质过氧化的敏感性与MLSP呈负相关。基于气相色谱和质谱分析，所有这些物种的肝脏蛋白质都含有丙二醛 - 赖氨酸和Nε-羧甲基赖氨酸加合物，这是蛋白质脂氧化的两个生物标志物。丙二醛 - 赖氨酸和Nε-羧甲基赖氨酸的稳态水平与过氧化指数直接相关，与MLSP呈负相关。我们认为，长寿哺乳动物可能选择了低程度的脂肪酸不饱和度，以保护其组织脂质和蛋白质免受氧化损伤，同时维持适合膜功能的环境。
