Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow region, Russia.
Scientific and Educational Center in Chernogolovka of Moscow Region State University, Mytishchi, Moscow region, Russia.
Bull Exp Biol Med. 2020 Jun;169(2):249-253. doi: 10.1007/s10517-020-04861-2. Epub 2020 Jul 10.
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.
我们测定了体内耐药鼠 P388 白血病株细胞中的 ROS 和丙二醛含量。结果发现，丙二醛浓度在各株间没有差异，但环磷酰胺耐药株（P388/CP）细胞内 ROS 浓度高于原始株（P388）和其他研究株（P388/Rub、P388/cPt）。细胞中转录因子 Nrf2 的核定位表明其持续激活。所有研究耐药株中均发现 GCLM 基因的相对表达增强；仅在环磷酰胺耐药株细胞中 GSR 和 GPX1 基因表达增加。这些发现表明，P388/CP 株的耐药机制与谷胱甘肽代谢活性增加有关，这种增加是由于抗氧化反应转录因子 Nrf2 的激活，而 ROS 细胞内浓度较高则是其背景。
