Rouen-Normandie University, UNIROUEN, INSERM, U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, 76821 Mont-Saint-Aignan, France; Institute for Research and Innovation in Biomedicine of Normandy, 76000 Rouen, France.
Rouen-Normandie University, UNIROUEN, INSERM, U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, 76821 Mont-Saint-Aignan, France; Institute for Research and Innovation in Biomedicine of Normandy, 76000 Rouen, France.
Free Radic Biol Med. 2018 Nov 1;127:145-152. doi: 10.1016/j.freeradbiomed.2018.05.076. Epub 2018 May 22.
Selenoprotein T (SELENOT, SELT) is a thioredoxin-like enzyme anchored at the endoplasmic reticulum (ER) membrane, whose primary structure is highly conserved during evolution. SELENOT is abundant in embryonic tissues and its activity is essential during development since its gene knockout in mice is lethal early during embryogenesis. Although its expression is repressed in most adult tissues, SELENOT remains particularly abundant in endocrine organs such as the pituitary, pancreas, thyroid and testis, suggesting an important role of this selenoprotein in hormone production. Our recent studies showed indeed that SELENOT plays a key function in insulin and corticotropin biosynthesis and release by regulating ER proteostasis. Although SELENOT expression is low or undetectable in most cerebral structures, its gene conditional knockout in brain provokes anatomical alterations that impact mice behavior. This suggests that SELENOT also plays an important role in brain development and function. In addition, SELENOT is induced after injury in brain or liver and exerts a cytoprotective effect. Thus, the data gathered during the last ten years of intense investigation of this newly discovered thioredoxin-like enzyme point to an essential function during development and in adult endocrine organs or lesioned brain, most likely by regulating ER redox circuits that control homeostasis and survival of cells with intense metabolic activity.
硒蛋白 T（SELENOT，SELT）是一种锚定在内质网（ER）膜上的硫氧还蛋白样酶，其一级结构在进化过程中高度保守。SELENOT 在胚胎组织中含量丰富，其活性在发育过程中至关重要，因为其在小鼠中的基因敲除在胚胎发生早期是致命的。尽管其在大多数成年组织中的表达受到抑制，但 SELENOT 在内分泌器官如垂体、胰腺、甲状腺和睾丸中仍然特别丰富，这表明这种硒蛋白在激素产生中具有重要作用。我们最近的研究确实表明，SELENOT 通过调节 ER 蛋白稳态在胰岛素和促肾上腺皮质激素的生物合成和释放中发挥关键作用。尽管 SELENOT 在大多数大脑结构中的表达较低或无法检测到，但它在大脑中的基因条件性敲除会引起影响小鼠行为的解剖学改变。这表明 SELENOT 也在大脑发育和功能中发挥重要作用。此外，SELENOT 在脑或肝损伤后被诱导，并发挥细胞保护作用。因此，在过去十年对这种新发现的硫氧还蛋白样酶进行的密集研究中收集的数据表明，它在发育过程中和成年内分泌器官或受损大脑中具有重要功能，很可能通过调节 ER 氧化还原电路来控制具有强烈代谢活性的细胞的内稳态和存活。
