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—Pregnan X receptor (PXR) is a nuclear receptor that plays an important role in the regulation of the expression enzymes of biotransformation and metabolism. The functioning and possible mechanisms of PXR regulation under conditions of nitrosative stress have not been studied yet and this was the purpose of this study. Nitrosative stress (NS) was modeled in Caco-2 cells, which were incubated in the presence of 1 μM, 10 μM, 50 μM, 100 μM, and 500 μM concentrations of S-nitrosoglutathione (GSNO) for 3 h, 24 h, and 72 h. The amount of PXR was assessed by Western blotting. Incubation of Caco-2 cells with all GSNO concentrations for 3 h led to a decrease in the amount of PXR. Incubation with GSNO (1−50 μM) for 24 h was accompanied by an increase in the amount of PXR, while at a higher concentration (100 μM) this indicator did not significantly differ from the control and at a concentration of 500 μM it was below the control level. Prolonged incubation (for 72 h) enhanced NS and led to a normalization (1 μM GSNO) or a decrease of the PXR level (10−500 μM GSNO). Bityrosine formed during NS induced PXR expression at concentrations of 0.4 mM and 1 mM.
"Biochemistry (Moscow), Supplement Series B:Biomedical Chemistry" – Springer Journals
Published: Jun 1, 2022
Keywords: pregnan X receptor; nitrosative stress; nitrosoglutathione; Caco-2 cell line
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