Bello Rosario I, Gómez-Díaz Consuelo, Burón María I, Navas Plácido, Villalba José M
Departamento de Biología Celular, Fisiología e Inmunología, Facultad de Ciencias, Universidad de Córdoba, Córdoba 14014, Spain.
Exp Gerontol. 2006 Nov;41(11):1174-84. doi: 10.1016/j.exger.2006.08.012. Epub 2006 Oct 17.
In this work we have studied how dietary fat affects aging-related changes in a number of factors that regulate rat hepatic apoptosis. Animals were fed lifelong with two experimental diets containing either virgin olive oil or sunflower oil as dietary fat. Caspases of the intrinsic and extrinsic pathways of apoptosis, Bcl-2 and Bax polypeptide levels, and plasma membrane neutral sphingomyelinase activity were determined at 6, 12, and 24 months of age. Caspase-8/10 activity (a marker of the extrinsic pathway) was not affected by either aging or dietary fat, but activities of both caspase-9 (a marker of the intrinsic pathway) and caspase-3 (an executioner caspase) were significantly depressed in liver from animals fed on a sunflower oil-based diet. These decreases were not observed in animals fed with a diet based on virgin olive oil, which also resulted in significantly lower Bcl-2/Bax ratios. On the other hand, in comparison with sunflower, dietary olive oil decreased oxidative stress in liver from aged rats, resulting in lower levels of membrane hydroperoxides and higher coenzyme Q levels in plasma membrane. Plasma membrane Mg(2+)-dependent neutral sphingomyelinase was strongly activated in aged rats fed on the sunflower oil diet, but no aging-related increase was observed in animals fed on the olive oil diet. Our results support that dietary oil can alter significantly the susceptibility of hepatocytes to different apoptotic stimuli by altering both pro- and anti-apoptotic mediators, which reinforces the importance of the diet in aging studies. Because virgin olive oil may increase susceptibility of hepatocytes to apoptosis induced through the intrinsic pathway under conditions of decreased oxidative stress, our results may have important implications to understand the potential beneficial effects of that edible oil against liver carcinogenesis during aging.
在本研究中，我们探究了膳食脂肪如何影响一些调节大鼠肝脏细胞凋亡的衰老相关变化。动物终身喂食两种分别以初榨橄榄油或葵花籽油作为膳食脂肪的实验性饮食。在6个月、12个月和24个月龄时，测定凋亡内源性和外源性途径的半胱天冬酶、Bcl-2和Bax多肽水平以及质膜中性鞘磷脂酶活性。半胱天冬酶-8/10活性（外源性途径的标志物）不受衰老或膳食脂肪的影响，但在以葵花籽油为基础饮食喂养的动物肝脏中，半胱天冬酶-9（内源性途径的标志物）和半胱天冬酶-3（执行性半胱天冬酶）的活性均显著降低。在以初榨橄榄油为基础饮食喂养的动物中未观察到这些降低，这也导致了显著更低的Bcl-2/Bax比率。另一方面，与葵花籽油相比，膳食橄榄油降低了老年大鼠肝脏中的氧化应激，导致质膜中膜氢过氧化物水平降低和辅酶Q水平升高。在以葵花籽油饮食喂养的老年大鼠中，质膜Mg(2+)依赖性中性鞘磷脂酶被强烈激活，但在以橄榄油饮食喂养的动物中未观察到与衰老相关的增加。我们的结果支持膳食油可通过改变促凋亡和抗凋亡介质，显著改变肝细胞对不同凋亡刺激的易感性，这强化了饮食在衰老研究中的重要性。由于初榨橄榄油可能在氧化应激降低的条件下增加肝细胞对通过内源性途径诱导的凋亡的易感性，我们的结果可能对理解该食用油在衰老过程中对肝癌发生的潜在有益作用具有重要意义。
