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Nrf2-Dependent Expression of Glutathione Antioxidant System Genes and Redox Status in Cells of In Vivo Drug-Resistant Murine P388 Leukemia Strains
Bulletin of Experimental Biology and Medicine ( IF 0.7 ) Pub Date : 2020-06-01 , DOI: 10.1007/s10517-020-04861-2
A A Balakina 1, 2 , T A Raevskaya 1 , V S Pavlov 1, 3 , V A Mumyatova 1, 2 , S A Goncharova 1 , A A Terent'ev 1, 2, 3
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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.

中文翻译:

谷胱甘肽抗氧化系统基因和氧化还原状态在体内耐药鼠 P388 白血病菌株细胞中的 Nrf2 依赖性表达

我们测量了体内耐药鼠 P388 白血病菌株细胞中 ROS 和丙二醛的含量。发现菌株在丙二醛浓度方面没有差异,但环磷酰胺抗性菌株(P388/CP)的细胞内ROS浓度高于原始(P388)和其他研究菌株(P388/Rub)的细胞, P388/cPt)。转录因子 Nrf2 在 P388/CP 菌株细胞中的核定位证明其组成型激活。在所有研究的耐药菌株中发现 GCLM 基因的相对表达增强;GSR 和 GPX1 基因的表达仅在环磷酰胺抗性菌株的细胞中增加。
更新日期:2020-06-01
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