Lebiedzińska Magdalena, Suski Jan, Duszyński Jerzy, Wieckowski Mariusz R
Pracownia Bioenergetyki i Błon Biologicznych, Instytut Biologii Doświadczalnej PAN, im. Marcelego Nenckiego, Warszawa.
Postepy Biochem. 2010;56(2):165-73.
The p66Shc adaptor protein has been in the spotlight of many researchgroups around the world for over adecade. Experiments conducted inrecent years unraveled its structure and enabled the recognition of basic cellular functions. Despite an undoubtedly tremendous progress in the characterization of p66Shc, mechanisms through which this protein potentially impacts the metabolism of mitochondria, and thus the cellular energetics are still waiting to be elucidated. Particularly interesting and profoundly studied is the concept that p66Shc may be a key component of the cell response to oxidative stress which may effectively contribute to the lifespan of the organism. p66Shc phosphorylation at serine 36 triggers a cascade of events leading to an increase in reactive oxygen species (ROS) production. The widely accepted free radical theory of ageing, proposed by Harman inthe - 1950s, assumes that an uncontrolled increase of ROS may lead to oxidation of fundamental cellular components such as proteins and phospholipids even sometimes premature dand cause DNA damage. Accumulation of such lesions in cells may unfavorably affect the functions of tissues and organs, leading to pathologies oreath of the organism. Although well experimentally established, knowledge regarding the involvement of the p66Shc protein in the production of ROS and its impact on the lifespan of organisms remains insufficient and requires a lot of additional research. Further investigation will permit a better understanding ofthe mechanisms governing the processes o f aging andthe emergence of variouspathologies associated with oxidative stress. This work is an attempt to systematize the existing knowledge about the p66Shc protein structure and functions. Another objective was to draw attention to the most interesting aspects and results of in vivo and in vitro studies in different models in the context of oxidative stress-associated pathologies and in aging.
十多年来,p66Shc衔接蛋白一直是全球众多研究团队关注的焦点。近年来进行的实验揭示了其结构,并使其基本细胞功能得以明确。尽管在p66Shc的特性描述方面无疑取得了巨大进展,但该蛋白潜在影响线粒体代谢,进而影响细胞能量代谢的机制仍有待阐明。特别有趣且深入研究的一个概念是,p66Shc可能是细胞对氧化应激反应的关键组成部分,这可能对生物体的寿命产生有效影响。丝氨酸36位点的p66Shc磷酸化会引发一系列事件,导致活性氧(ROS)生成增加。哈曼在20世纪50年代提出的被广泛接受的衰老自由基理论认为,ROS的不受控制增加可能导致蛋白质和磷脂等基本细胞成分的氧化,甚至有时会导致DNA损伤。细胞中此类损伤的积累可能对组织和器官的功能产生不利影响,导致机体患病或死亡。尽管已通过实验充分证实,但关于p66Shc蛋白参与ROS生成及其对生物体寿命影响的知识仍然不足,需要大量额外研究。进一步的研究将有助于更好地理解衰老过程的调控机制以及与氧化应激相关的各种疾病的发生。这项工作旨在对关于p66Shc蛋白结构和功能的现有知识进行系统化整理。另一个目标是在与氧化应激相关的疾病和衰老背景下,提请人们关注不同模型中体内和体外研究中最有趣的方面和结果。