Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Free Radic Biol Med. 2021 Feb 1;163:255-267. doi: 10.1016/j.freeradbiomed.2020.12.027. Epub 2020 Dec 28.
Liver regeneration is a remarkably complex phenomenon conserved across all vertebrates, enabling the restoration of lost liver mass in a matter of days. Unfortunately, extensive damage to the liver may compromise this process, often leading to the death of affected individuals. Ischemia/reperfusion injury (IRI) is a common source of damage preceding regeneration, often present during liver transplantation, resection, trauma, or hemorrhagic shock. Increased oxidative stress and mitochondrial dysfunction are key hallmarks of IRI, which can jeopardize the liver's ability to regenerate. Therefore, a better understanding of both liver regeneration and IRI is of important clinical significance. In the current review, we discuss the potential role of sestrin 2 (SESN2), a novel anti-aging protein, in liver regeneration and ischemia/reperfusion preceding regeneration. We highlight its beneficial role in protecting cells from mitochondrial dysfunction and oxidative stress as key aspects of its involvement in liver regeneration. Additionally, we describe how its ability to promote the expression of Nrf2 bears significant importance in this context. Finally, we focus on a potential novel link between SESN2, mitohormesis and ischemic preconditioning, which could explain some of the protective effects of preconditioning.
肝脏再生是一种在所有脊椎动物中都保守的非常复杂的现象，它能够在几天内恢复失去的肝脏质量。不幸的是，肝脏的广泛损伤可能会影响这个过程，这往往会导致受影响个体的死亡。缺血/再灌注损伤（IRI）是再生前常见的损伤来源，常发生于肝移植、肝切除、创伤或失血性休克期间。氧化应激和线粒体功能障碍的增加是 IRI 的主要特征，这可能危及肝脏的再生能力。因此，更好地了解肝脏再生和 IRI 具有重要的临床意义。在当前的综述中，我们讨论了新型抗衰老蛋白 sestrin 2（SESN2）在肝脏再生和缺血/再灌注损伤之前的再生中的潜在作用。我们强调了它在保护细胞免受线粒体功能障碍和氧化应激方面的有益作用，这是其参与肝脏再生的关键方面。此外，我们还描述了它促进 Nrf2 表达的能力在这方面的重要意义。最后，我们关注了 SESN2、mitohormesis 和缺血预处理之间的一个潜在的新联系，这可以解释预处理的一些保护作用。
