Nrf2-Dependent Expression of Glutathione Antioxidant System Genes and Redox Status in Cells of In Vivo Drug-Resistant Murine P388 Leukemia Strains.

Abstract:

:We measured the content of ROS and malondialdehyde in cells of in vivo drug-resistant murine P388 leukemia strains. It was found that the strains did not differ by malondialdehyde concentration, but intracellular concentration of ROS in cells of the cyclophosphamide-resistant strain (P388/CP) was higher than in cells of the original (P388) and other studied strains (P388/Rub, P388/cPt). Nuclear localization of the transcription factor Nrf2 in cells of strain P388/CP attested to its constitutive activation. Enhanced relative expression of the GCLM gene was found in all studied drug-resistant strains; the expression of the GSR and GPX1 genes was increased only in cells of the cyclophosphamide-resistant strain. These findings suggest that the mechanism of resistance of strain P388/CP is associated with increased activity of glutathione metabolism that developed as a result of activation of the antioxidant response transcription factor Nrf2 against the background of high intracellular concentration of ROS.

journal_name

Bull Exp Biol Med

authors

Balakina AA,Raevskaya TA,Pavlov VS,Mumyatova VA,Goncharova SA,Terent'ev AA

doi

10.1007/s10517-020-04861-2

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

249-253

issue

2

eissn

0007-4888

issn

1573-8221

pii

10.1007/s10517-020-04861-2

journal_volume

169

pub_type

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