Herrero A, Portero-Otín M, Bellmunt M J, Pamplona R, Barja G
Department of Animal Biology-II (Animal Physiology), Faculty of Biology, Complutense University, Madrid 28040, Spain.
Mech Ageing Dev. 2001 Apr 15;122(4):427-43. doi: 10.1016/s0047-6374(01)00214-7.
Previous comparative studies have shown that long-lived animals have lower fatty acid double bond content in their mitochondrial membranes than short-lived ones. In order to ascertain whether this trait protects mitochondria by decreasing lipid and protein oxidation and oxygen radical generation, the double bond content of rat heart mitochondrial membranes was manipulated by chronic feeding with semi-purified AIN-93G diets rich in highly unsaturated (UNSAT) or saturated (SAT) oils. UNSAT rat heart mitochondria had significantly higher double bond content and lipid peroxidation than SAT mitochondria. They also showed increased levels of the markers of protein oxidative damage malondialdehyde-lysine, protein carbonyls, and N(e)-(carboxymethyl)lysine adducts. Basal rates of mitochondrial oxygen radical generation were not modified by the degree of fatty acid unsaturation, but the rates of H2O2 generation stimulated by antimycin A were higher in UNSAT than in SAT mitochondria. These results demonstrate that increasing the degree of fatty acid unsaturation of heart mitochondria increases oxidative damage to their lipids and proteins, and can also increase their rates of mitochondrial oxygen radical generation in situations in which the degree of reduction of Complex III is higher than normal. These observations strengthen the notion that the relatively low double bond content of the membranes of long-lived animals could have evolved to protect them from oxidative damage.
以往的比较研究表明，长寿动物线粒体膜中的脂肪酸双键含量低于短寿动物。为了确定这一特性是否通过减少脂质和蛋白质氧化以及氧自由基生成来保护线粒体，通过长期喂食富含高度不饱和（UNSAT）或饱和（SAT）油的半纯化AIN - 93G饮食来控制大鼠心脏线粒体膜的双键含量。与SAT线粒体相比，UNSAT大鼠心脏线粒体的双键含量和脂质过氧化水平显著更高。它们还显示出蛋白质氧化损伤标志物丙二醛 - 赖氨酸、蛋白质羰基和N（e） - （羧甲基）赖氨酸加合物的水平升高。线粒体氧自由基生成的基础速率不受脂肪酸不饱和度的影响，但抗霉素A刺激的H2O2生成速率在UNSAT线粒体中高于SAT线粒体。这些结果表明，增加心脏线粒体脂肪酸不饱和度会增加其脂质和蛋白质的氧化损伤，并且在细胞色素c氧化酶复合体III还原程度高于正常的情况下，还会增加其线粒体氧自由基生成速率。这些观察结果强化了这样一种观点，即长寿动物膜中相对较低的双键含量可能已经进化出来以保护它们免受氧化损伤。
