Pregnan X Receptor Functioning under Conditions of Nitrosative Stress

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2022-05-17 DOI:10.1134/S1990750822020020

Y. V. Abalenikhina, E. A. Sudakova, A. A. Seidkulieva, A. V. Shchulkin, E. N. Yakusheva

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Abstract—

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.

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亚硝化应激条件下妊娠X受体的功能

摘要妊娠X受体(pregnan X receptor, PXR)是一种核受体，在生物转化和代谢的表达酶调控中起重要作用。在亚硝化胁迫条件下，PXR调控的功能和可能的机制尚未得到研究，这也是本研究的目的。以Caco-2细胞为模型，分别在1 μM、10 μM、50 μM、100 μM和500 μM浓度的s -亚硝基谷胱甘肽(S-nitrosoglutathione, GSNO)作用下培养3 h、24 h和72 h, Western blotting检测PXR的表达量。Caco-2细胞与所有GSNO浓度孵育3 h后，PXR的含量均有所下降。与GSNO (1 ~ 50 μM)孵育24 h后，PXR的含量有所增加，但在100 μM浓度下，PXR的含量与对照无显著差异，500 μM浓度下PXR的含量低于对照。延长孵育时间(72h)可增强NS，导致PXR水平降低(10 ~ 500 μM GSNO)或正常化(1 μM GSNO)。在0.4 mM和1mm浓度下，NS诱导PXR表达时形成Bityrosine。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.