School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Student Research Committee, Health Research Center, Babol University of Medical Sciences, Babol, Iran.
Oxid Med Cell Longev. 2021 Nov 2;2021:8790369. doi: 10.1155/2021/8790369. eCollection 2021.
Sestrin2 is a stress-inducible metabolic regulator and a conserved antioxidant protein which has been implicated in the pathogenesis of several diseases. Sestrin2 can protect against atherosclerosis, heart failure, hypertension, myocardial infarction, stroke, spinal cord injury neurodegeneration, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, acute kidney injury (AKI), chronic kidney disease (CKD), and pulmonary inflammation. Oxidative stress and cellular damage signals can alter the expression of Sestrin2 to compensate for organ damage. Different stress signals such as those mediated by P53, Nrf2/ARE, HIF-1, NF-B, JNK/c-Jun, and TGF-/Smad signaling pathways can induce Sestrin2 expression. Subsequently, Sestrin2 activates Nrf2 and AMPK. Furthermore, Sestrin2 is a major negative regulator of mTORC1. Sestrin2 indirectly regulates the expression of several genes and reprograms intracellular signaling pathways to attenuate oxidative stress and modulate a large number of cellular events such as protein synthesis, cell energy homeostasis, mitochondrial biogenesis, autophagy, mitophagy, endoplasmic reticulum (ER) stress, apoptosis, fibrogenesis, and lipogenesis. Sestrin2 vigorously enhances M2 macrophage polarization, attenuates inflammation, and prevents cell death. These alterations in molecular and cellular levels improve the clinical presentation of several diseases. This review will shed light on the beneficial effects of Sestrin2 on several diseases with an emphasis on underlying pathophysiological effects.
Sestrin2 是一种应激诱导的代谢调节剂和保守的抗氧化蛋白，与多种疾病的发病机制有关。Sestrin2 可以预防动脉粥样硬化、心力衰竭、高血压、心肌梗死、中风、脊髓损伤、神经退行性变、非酒精性脂肪性肝病 (NAFLD)、肝纤维化、急性肾损伤 (AKI)、慢性肾脏病 (CKD) 和肺部炎症。氧化应激和细胞损伤信号可以改变 Sestrin2 的表达，以补偿器官损伤。不同的应激信号，如 P53、Nrf2/ARE、HIF-1、NF-B、JNK/c-Jun 和 TGF-/Smad 信号通路介导的信号，可以诱导 Sestrin2 的表达。随后，Sestrin2 激活 Nrf2 和 AMPK。此外，Sestrin2 是 mTORC1 的主要负调控因子。Sestrin2 间接调节几种基因的表达，并重新编程细胞内信号通路，以减轻氧化应激并调节大量细胞事件，如蛋白质合成、细胞能量稳态、线粒体生物发生、自噬、线粒体自噬、内质网 (ER) 应激、细胞凋亡、纤维化和脂肪生成。Sestrin2 有力地增强了 M2 巨噬细胞极化，减轻了炎症反应，防止了细胞死亡。这些分子和细胞水平的改变改善了多种疾病的临床表现。本综述将重点介绍 Sestrin2 对多种疾病的有益影响及其潜在的病理生理作用。
