[Mechanism of regulation of the constitutive androstane receptor under conditions of modeling oxidative stress in vitro]

Biomed Khim. 2022 Aug;68(4):297-301. doi: 10.18097/PBMC20226804297.
[Article in Russian]

Abstract

The constitutive androstane receptor (CAR) is a nuclear receptor that participates in the regulation of biotransformation of toxic substances and metabolic processes. The mechanisms of expression changes of CAR under conditions of oxidative stress (OS) have not been studied yet and this was the purpose of the study. OS was modeled by incubating Caco2 cells with hydrogen peroxide 10-100 μM for 72 h. The amount of CAR was determined by the Western blot, nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by a heterogeneous enzyme immunoassay malondialdehyde (MDA), the lipid peroxidation products (LPP) was assayed by a photometric method. Incubation of cells with 10 μM and 50 μM H2O2 led to an increase in the amount of CAR and Nrf2, while incubation with 100 μM H2O2 caused their decrease. Nrf2 inhibition did not influence the CAR content under OS conditions. 10 μM MDA increased the CAR content, 100 μM MDA had no effect, while 150 μM reduced the amount of CAR.

Konstitutivnyĭ androstanovyĭ retseptor (CAR) — iadernyĭ retseptor, kotoryĭ uchastvuet v reguliatsii biotransformatsii toksicheskikh veshchestv i metabolicheskikh protsessov. Mekhanizmy izmeneniia kolichestva CAR v usloviiakh okislitel'nogo stressa (OS) na dannyĭ moment ne izucheny, chto i posluzhilo tsel'iu issledovaniia. OS modelirovali, inkubiruia kletki linii Saso-2 s N2O2 10 mkM, 50 mkM i 100 mkM v techenie 72 ch. Kolichestvo CAR opredeliali metodom vestern-blot, iadernogo faktora éritroidnogo proiskhozhdeniia 2 (Nrf2) — geterogennym immunofermentnym analizom, kontsentratsiiu produktov perekisnogo okisleniia lipidov (POL) — fotometricheskim metodom. Inkubirovanie kletok s N2O2 v kontsentratsiiakh 10 mkM i 50 mkM privodilo k uvelicheniiu kolichestva CAR i Nrf2, a pri 100 mkM — k ikh snizheniiu. Pri ingibirovanii Nrf2 dinamika soderzhaniia CAR v usloviiakh OS ne izmenialas'. MDA v kontsentratsii 10 mkM povyshal, v kontsentratsii 100 mkM ne vliial, v kontsentratsii 150 mkM snizhal kolichestvo CAR.

Keywords: cells of the Caco2 line; constitutive androstane receptor (CAR); malondialdehyde; nuclear factor erythroid 2-related factor 2 (Nrf2); oxidative stress.

MeSH terms

  • Caco-2 Cells
  • Constitutive Androstane Receptor*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress

Substances

  • Constitutive Androstane Receptor
  • NF-E2-Related Factor 2
  • Hydrogen Peroxide