Migliaccio Enrica, Giorgio Marco, Pelicci Pier Giuseppe
Experimental Oncology Department, European Institute of Oncology, Milan, Italy.
Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):600-8. doi: 10.1089/ars.2006.8.600.
p66Shc was the first mammalian gene whose mutation was demonstrated to increase resistance to oxidative stress and to prolong life span. Many hypotheses have been formulated to explain the biochemical and molecular basis of mammalian aging. Among them the free radical theory of aging, which was first proposed half a century ago by Harman, has received much attention by biomedical scientists. This theory proposed that, because of their high reactivity, reactive oxygen species (ROS) would lead to unavoidable and potentially deleterious by-products, and such an increasingly damaging process could be responsible for degenerative diseases and aging. Recent reports suggest an important role of p66Shc protein in the regulation of cellular responses to oxidative stress, apoptosis, and aging. In this review we discuss what has been discovered about p66Shc in the past 10 years and we focus particularly on its role in ROS regulation, which appears to be extremely promising to define mammalian aging processes.
p66Shc是首个被证明其突变可增强对氧化应激的抵抗力并延长寿命的哺乳动物基因。人们已提出许多假说来解释哺乳动物衰老的生化和分子基础。其中，半个世纪前由哈曼首次提出的衰老自由基理论受到了生物医学科学家的广泛关注。该理论认为，由于活性氧（ROS）具有高反应性，它们会导致不可避免且可能有害的副产物，而这种日益具有破坏性的过程可能是退行性疾病和衰老的原因。最近的报道表明p66Shc蛋白在调节细胞对氧化应激、细胞凋亡和衰老的反应中起着重要作用。在这篇综述中，我们讨论了过去10年中关于p66Shc的发现，尤其关注其在ROS调节中的作用，这似乎对于界定哺乳动物衰老过程极具前景。
