Selenoprotein P regulation by the glucocorticoid receptor

Abstract

Maintenance of the antioxidant activity of selenoproteins is one potential mechanism of the beneficial health effects of selenium. Selenoprotein P is the primary selenium distribution protein of the body as well as the major selenium containing protein in serum. The transcriptional regulation of selenoprotein P is of interest since the extrahepatic expression of this gene has demonstrated differentiation-dependent expression in development as well as under different disease states. SEPP1 displays patterned expression in numerous tissues during development and the loss of SEPP1 expression has been observed in malignancy. In addition, factors that influence inflammatory processes like cytokines and their regulators have been implicated in selenoprotein P transcriptional control. Herein, we identify a retinoid responsive element and describe a mechanism where the glucocorticoid receptor negatively regulates expression of selenoprotein P. Luciferase reporter assays and quantitative PCR were used to measure selenoprotein P transcription in engineered HEK-293 cells. When stimulated with ecdysone analogs, selenoprotein P expression was increased with the use of a fusion transcription factor that contains the glucocorticoid receptor DNA binding domain, an ecdysone ligand-binding domain, and a strong transactivation domain as well as the retinoid X receptor. The native glucocorticoid receptor inhibited selenoprotein P transactivation, and selenoprotein P was further attenuated in the presence of dexamethasone. Our results may provide insight into a potential mechanism by which selenium is redistributed during development, differentiation or under conditions of critical illness, where glucocorticoid levels are typically increased.

Selenoprotein P protects cells from lipid hydroperoxides generated by 15-LOX-1

“…SelP was derived from the supernatant of ponasterone A treated 293-EcR cells. Transcription and translation of SelP has previously been shown to increase in these cells when the VgEcR gene expression system is activated by ponasterone A [29]. Microarray results do not support changes in the expression of other selenoproteins under these conditions (data not shown); therefore, SelP is the only selenoprotein expected to be enriched in the concentrated supernatant collected from these cells.…”

“…Increased transcription and translation of SelP has previously been observed in 293-EcR cells treated with the ecydsone analog ponasterone A (PonA) [29]. 293-EcR cells were maintained in serum-free CD-293 cell culture medium supplemented with 2mM L-glutamine, 1 μM sodium selenite and 10 μM PonA.…”

Stress–response pathways are altered in the hippocampus of chronic alcoholics

“…Five genes were identified in 4 studies, and are thus strong candidates for further study: selenoprotein P ( SEPP1 ), heterochromatin protein 1 binding protein 3 ( HP1BP3 ), transferrin ( TF ), EGF-like repeats and discoidin I-like domains 3 ( EDIL3 ), and contactin associated proteinlike 2 (CNTNAP2). SEPP1 binds selenium and has antioxidant activity and is down-regulated by both inflammatory cytokines like IL1β (Dreher et al, 1997) and glucocorticoids (Rock & Moos, 2009); it is decreased in the hippocampi of alcoholics (Supplementary Table S2). Transferrin is an iron transporter and is also a negative acute phase response protein; it is also decreased.…”

Intrauterine Growth Restriction Modifies the Developmental Pattern of Intestinal Structure, Transcriptomic Profile, and Bacterial Colonization in Neonatal Pigs

“…These modifications that were evident throughout the entire experimental period for protein and glucose metabolism and from d 2 for lipid metabolism may participate in variations in energy expenditure and nutrient utilization in neonates with IUGR (42). Moreover, the postnatal increase in PTGS2, RPS2, APOA1, SEPP1, and TLR3 and the decrease in VCP expression in ileum (43)(44)(45)(46)(47)(48), and the increase in GPR65 and TIMP1 and decrease in CASP7 expression in the colon (49-51) may be consequences of the increased exposure of fetuses with IUGR to glucocorticoids, as reported (32,33).…”