Sorbonne Universités, UPMC Univ Paris 06, UMR 8256, Biological adaptation and ageing-IBPS, F-75005 Paris, France; CNRS UMR 8256, F-75005 Paris, France; INSERM U1164, F-75005 Paris, France.
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Mech Ageing Dev. 2018 Mar;170:59-71. doi: 10.1016/j.mad.2017.07.005. Epub 2017 Jul 27.
Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the "Oxi-proteome") during ageing and age-related diseases represent a restricted set of cellular proteins, indicating that certain proteins are more prone to oxidative carbonylation and subsequent intracellular accumulation. The occurrence of specific carbonylated proteins upon oxidative stress induced premature senescence of WI-38 human fibroblasts and their follow-up identification have been addressed in this study. Indeed, it was expected that the identification of these proteins would give insights into the mechanisms by which oxidatively damaged proteins could affect cellular function. Among these proteins, some are belonging to the cytoskeleton while others are mainly involved in protein quality control and/or biosynthesis as well as in redox and energy metabolism, the impairment of which has been previously associated with cellular ageing. Interestingly, the majority of these carbonylated proteins were found to belong to functional interaction networks pointing to signalling pathways that have been implicated in the oxidative stress response and subsequent premature senescence.
氧化损伤蛋白质的积累是细胞和机体衰老的一个标志，也是人类成纤维细胞复制性衰老和应激诱导性早衰的共同表型特征。此外，在衰老和与年龄相关的疾病过程中积累的氧化蛋白（即“氧化蛋白质组”）代表了一组受限的细胞蛋白，表明某些蛋白质更容易发生氧化羰基化和随后的细胞内积累。本研究探讨了 WI-38 人成纤维细胞氧化应激诱导性早衰过程中特定羰基化蛋白的发生及其后续鉴定。事实上，人们期望这些蛋白质的鉴定能够深入了解氧化损伤蛋白如何影响细胞功能的机制。在这些蛋白质中，一些属于细胞骨架，而另一些主要参与蛋白质质量控制和/或生物合成以及氧化还原和能量代谢，这些功能的损伤先前与细胞衰老有关。有趣的是，大多数这些羰基化蛋白属于功能相互作用网络，这些网络指向与氧化应激反应和随后的早衰相关的信号通路。
