Thyroid Research Unit, Icahn School of Medicine at Mount Sinai, and the James J. Peters VA Medical Center, New York, New York.
J Clin Endocrinol Metab. 2020 Mar 1;105(3):e66-9. doi: 10.1210/clinem/dgz193.
Understanding the regulatory mechanisms that control intracellular stress has fundamental importance since its failure results in cell death. Evidence has emerged indicating that the intracellular signals that are induced in response to diverse stresses include the deoxyribonucleic acid damage response, the unfolded protein response, the mitochondrial and/or endoplasmic reticulum stress responses, and the autophagy signals to degrade dangerous protein aggregates. These signals bring changes to the stressed cells that may support systemic homeostasis or contribute to disease pathology. In normal thyroid cells, both reactive oxygen species (ROS) and antioxidant (AOD) activity is low. An increase in ROS balanced by AOD leads only to mild inflammation, but unopposed increases in ROS lead to a strong inflammatory response and may result in apoptosis. A balance between ROS and AOD is, therefore, needed to maintain thyrocyte homeostasis. This perspective describes how thyroid cells are subjected to multiple insults and how they try to protect themselves using these different cellular responses.
理解控制细胞内应激的调节机制至关重要,因为其失败会导致细胞死亡。有证据表明,细胞对各种应激的反应包括脱氧核糖核酸损伤反应、未折叠蛋白反应、线粒体和/或内质网应激反应以及自噬信号以降解危险的蛋白质聚集体。这些信号会给应激细胞带来变化,这些变化可能有助于维持全身的内稳态,也可能导致疾病的病理变化。在正常甲状腺细胞中,活性氧(ROS)和抗氧化(AOD)的活性都很低。ROS 的增加被 AOD 平衡只会导致轻度炎症,但 ROS 的无拮抗增加会导致强烈的炎症反应,并可能导致细胞凋亡。因此,需要在 ROS 和 AOD 之间取得平衡,以维持甲状腺细胞的内稳态。本文从多个方面描述了甲状腺细胞如何受到多种损伤,以及它们如何利用这些不同的细胞反应来保护自己。