Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.
Physiol Res. 2011;60(2):281-9. doi: 10.33549/physiolres.932019. Epub 2010 Nov 29.
Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15- and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions.
线粒体功能障碍和氧化损伤的积累被认为是衰老的主要因素。然而，关于线粒体电子传递链（ETC）复合物活性与年龄相关的变化的数据仍然存在争议，ETC 功能障碍的分子机制在很大程度上仍然未知。在这项研究中，我们研究了衰老对成年（6 个月大）、老年（15 个月大）和衰老（26 个月大）大鼠心脏线粒体中 ETC 复合物活性和蛋白质及脂质氧化损伤的影响。ETC 复合物 I-IV 的活性随年龄的增长呈现不同程度的抑制。其中，复合物 IV 的活性下降最为显著，而复合物 II 的活性在老年大鼠中保持不变，在衰老大鼠中仅略有下降。与成年大鼠相比，老年和衰老大鼠的心脏中丙二醛、4-羟基壬烯醛（HNE）和二酪氨酸的含量明显升高，而巯基含量减少。尽管 HNE 含量随年龄增长而显著增加（15 个月大和 26 个月大的大鼠分别增加了 25%和 76%），但 Western blot 分析仅显示出少量的 HNE-蛋白加合物。本研究表明，ETC 复合物活性的非均匀下降至少部分是由于线粒体氧化损伤所致；然而，脂质过氧化产物似乎对酶功能的影响有限。
