Selenocysteine β-lyase and its role in renal selenium homeostasis

Selenocysteine β-lyase (Scly) is a critical enzyme for selenoprotein synthesis. While its systemic role in metabolic health is emerging, its specific function in the kidney remains unexplored. To address this knowledge gap, we utilized a whole-body Scly knockout (KO) mouse model fed low and adequate selenite diets, and measured blood pressure using a Kent Scientific CODA2 system, harvested kidneys for histological, total selenium (Se) content and gene expression analysis, and collected urine to determine osmolality and Se levels using an osmometer and total reflection X-ray fluorescence (TXRF), respectively. Our preliminary findings reveal that Scly KO mice exhibited a modest increase in blood pressure, and Scly loss led to atrophic renal tubular structure. While the expression of key selenoprotein genes like glutathione peroxidase 1 and 3 remains unaffected, thioredoxin reductase 2 expression is upregulated and selenoprotein I expression is downregulated in Scly KO compared to WT mice. Despite these alterations in gene expression, urinary Se excretion and osmolality are comparable between the two groups. These results suggest that Scly plays a pivotal role in maintaining renal selenoprotein homeostasis and may contribute to the regulation of blood pressure. AS (NIH-2T32HL115505-11) and LS (NIH/NIDDK 1 R01 DK128390-01). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.