{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that the human selenoproteome, which comprises 25 distinct selenoproteins synthesized with the unique amino acid selenocysteine, plays diverse roles in cellular redox regulation and homeostasis. Among these, SELENOT has attracted attention as a redox-active protein and a member of this unique protein family, discovered through improved computational identification methods that distinguish UGA’s dual role in coding and termination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInvestigations in pancreatic islets have shown that SELENOT is a thioredoxin-like protein predominantly expressed in insulin- and somatostatin-producing cells. Functionally, conditional deletion of SELENOT in pancreatic β-cells in mice resulted in impaired glucose tolerance, a decrease in insulin secretion, and altered islet morphology, suggesting that SELENOT plays a critical role in modulating glucose homeostasis. Furthermore, its up-regulation by pituitary adenylate cyclase-activating polypeptide (PACAP) indicates that it may be a key mediator in a feed-forward mechanism to enhance insulin secretion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cardiac pathology, SELENOT has emerged as an important redox sensor in hypertrophied cardiomyocytes. A peptide mimicking its redox-active domain—PSELT—was shown to confer significant cardioprotection in models of heart failure by attenuating inflammation, reducing fibrosis, mitigating cellular damage, and improving contractile function. Moreover, the regulation of SELENOT production and secretion in response to hypertrophic stress suggests that it not only contributes to acute cell survival mechanisms but may also serve as a biomarker reflecting the extent of myocardial injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gregory V Kryukov, Sergi Castellano, Sergey V Novoselov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of mammalian selenoproteomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1083516"}], "href": "https://doi.org/10.1126/science.1083516"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12775843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12775843"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gaëtan Prevost, Arnaud Arabo, Long Jian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PACAP-regulated gene selenoprotein T is abundantly expressed in mouse and human β-cells and its targeted inactivation impairs glucose tolerance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2013-1167"}], "href": "https://doi.org/10.1210/en.2013-1167"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23913443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23913443"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anna De Bartolo, Teresa Pasqua, Naomi Romeo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-024-05192-w"}], "href": "https://doi.org/10.1186/s12967-024-05192-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38643121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38643121"}]}]}]}