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Effect of the Nitric Oxide Donor S-Nitrosoglutathione on Expression of the Constitutive Androstane Receptor

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Abstract

The mechanisms of regulation of the constitutive androstane receptor (CAR) under the effect of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO), added to a nutrient medium at concentrations ranging from 1 to 500 µM for 3, 24, and 72 h, were studied in vitro on Caco-2 cells. Relative CAR levels were assessed by Western blotting. It was found that short-term (3 and 24 h) exposure to GSNO at concentrations of 1–500 µM did not affect the relative CAR level, while after a 72-h exposure to GSNO concentrations of 1, 10 and 50 µM, it increased. Such an increase in the relative CAR level upon exposure to a low GSNO concentration (1 µM) was proved to be implemented via the NO-cGMP signaling pathway. Further increase in GSNO concentrations to 10 and 50 µM triggered the development of nitrosative stress, and the relative CAR level was regulated via the nitration product bityrosine. Nitrosative stress progression at GSNO concentrations of 100 and 500 µM was accompanied by a decline in Caco-2 cell survival, apparently due to the damage to the CAR molecule, leading to a decrease in the relative CAR level.

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Funding

The work was supported by the grant of the President of the Russian Federation (MK-1856.2020.7).

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Authors and Affiliations

  1. Pavlov Ryazan State Medical University, Ryazan, Russia

    Yu. V. Abalenikhina, E. A. Sudakova, А. А. Seidkuliyeva, A. V. Shchulkin & E. N. Yakusheva

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  1. Yu. V. Abalenikhina
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  2. E. A. Sudakova
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Contributions

Conceptualization and experimental design (A.V.S., Yu.V.A.); data collection (A.V.S., Yu.V.A., E.A.S., A.A.S.); data processing (A.V.S., Yu.V.A., E.A.S., A.A.S.); writing and editing the manuscript (A.V.S., Yu.V.A., E.N.Ya.).

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Correspondence to Yu. V. Abalenikhina.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2022, Vol. 58, No. 5, pp. 412–422https://doi.org/10.31857/S0044452922050023.

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Abalenikhina, Y.V., Sudakova, E.A., Seidkuliyeva, А.А. et al. Effect of the Nitric Oxide Donor S-Nitrosoglutathione on Expression of the Constitutive Androstane Receptor. J Evol Biochem Phys 58, 1341–1352 (2022). https://doi.org/10.1134/S0022093022050064

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