Rabbit Anti-Human PSTK Polyclonal antibody

Selenoproteins result from the incorporation of selenocysteine (Sec-U) at an UGA-stop codon positioned within a gene's open reading frame and directed by selenocysteine insertion sequence (SECIS) elements. Although the selenocysteine incorporation pathway has been identified in a wide range of organisms it has not yet been reported in the Kinetoplastida Leishmania and Trypanosoma. Here we present evidence consistent with the presence of a selenocysteine biosynthetic pathway in Kinetoplastida. These include the existence of SECIS-containing coding sequences in Leishmania major and Leishmania infantum, the incorporation of Se-75 into Leishmania proteins, the occurrence of selenocysteine-tRNA (tRNA(uca)(sec)) in both Leishmania and Trypanosoma and in addition the finding of all genes necessary for selenocysteine synthesis such as SELB, SELD, PSTK and SECp43. As in other eukaryotes, the Kinetoplastids have no identifiable SELA homologue. To our knowledge this is the first report on the identification of selenocysteme insertion machinery in Kinetoplastida, more specifically in Leishmania, at the sequence level. (c) 2006 Elsevier B.V. All rights reserved.

Background Selenium (Se) levels decrease in the circulation during acute inflammatory states and sepsis, and are inversely associated with morbidity and mortality. A more specific understanding of where selenoproteins and Se processing are compromised during insult is needed. We investigated the acute signaling response in selenoenzymes and Se processing machinery in multiple organs after innate immune activation in response to systemic lipopolysaccharide (LPS). Methods Wild type (WT) adult male C57/B6 mice were exposed to LPS (5 mg/kg, intraperitoneal). Blood, liver, lung, kidney and spleen were collected from control mice as well as 2, 4, 8, and 24 h after LPS. Plasma Se concentration was determined by ICP-MS. Liver, lung, kidney and spleen were evaluated for mRNA and protein content of selenoenzymes and proteins required to process Se. Results After 8 h of endotoxemia, plasma levels of Se and the Se transporter protein, SELENOP were significantly decreased. Consistent with this timing, the transcription and protein content of several hepatic selenoenzymes, including SELENOP, glutathione peroxidase 1 and 4 were significantly decreased. Furthermore, hepatic transcription and protein content of factors required for the Se processing, including selenophosphate synthetase 2 (Sps2), phosphoseryl tRNA kinase (Pstk), selenocysteine synthase (SepsecS), and selenocysteine lyase (Scly) were significantly decreased. Significant LPS-induced downregulation of these key selenium processing enzymes was observed in isolated hepatocytes. In contrast to the acute and dynamic changes observed in the liver, selenoenzymes did not decrease in the lung, kidney or spleen. Conclusion Hepatic selenoenzyme production and Se processing factors decreased after endotoxemia. This was temporally associated with decreased circulating Se. In contrast to these active changes in the regulation of Se processing in the liver, selenoenzymes did not decrease in the lung, kidney or spleen. These findings highlight the need to further study the impact of innate immune challenges on Se processing in the liver and the impact of targeted therapeutic Se replacement strategies during innate immune challenge.