对甲萘醌耐药的中国仓鼠卵巢细胞具有增强的谷胱甘肽合成能力。
Menadione-resistant Chinese hamster ovary cells have an increased capacity for glutathione synthesis.
作者信息
Vallis K A, Reglinski J, Garner M, Bridgeman M M, Wolf C R
机构信息
Imperial Cancer Research Fund Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK.
出版信息
Br J Cancer. 1997;76(7):870-7. doi: 10.1038/bjc.1997.477.
A cell line (MRc40) resistant to the model quinone compound, menadione, has been isolated from a parental Chinese hamster ovary cell line (CHO-K1). The known relationship between menadione toxicity and glutathione (GSH) depletion led us to investigate whether the mechanism of resistance of MRc40 was related to alteration in GSH homeostasis. Intracellular concentrations of GSH and cysteine (CySH) were twofold and 3.2-fold greater in MRc40 than in CHO-K1. Following exposure to menadione, GSH and CySH were depleted, but subsequent recovery of thiols was more rapid and of greater magnitude in MRc40 than in CHO-K1. Twelve hours after exposure to menadione, the concentrations of GSH and CySH were 9.7- and 4.2-fold greater in MRc40 than in CHO-K1. Using nuclear magnetic resonance (NMR) spectroscopy, we observed the in situ removal of menadione from cell suspensions of CHO-K1 and MRc40. However, only in CHO-K1 did we observe concomitant depletion of NMR-visible GSH. We conclude that the perturbation of GSH metabolism contributes to the resistant phenotype and is an important characteristic of menadione-resistant CHO cells.
已从亲本中国仓鼠卵巢细胞系（CHO-K1）中分离出对模型醌类化合物甲萘醌具有抗性的细胞系（MRc40）。甲萘醌毒性与谷胱甘肽（GSH）消耗之间的已知关系促使我们研究MRc40的抗性机制是否与GSH稳态的改变有关。MRc40细胞内GSH和半胱氨酸（CySH）的浓度分别比CHO-K1细胞高两倍和3.2倍。暴露于甲萘醌后，GSH和CySH被消耗，但随后MRc40细胞中硫醇的恢复比CHO-K1细胞更快且幅度更大。暴露于甲萘醌12小时后，MRc40细胞中GSH和CySH的浓度分别比CHO-K1细胞高9.7倍和4.2倍。使用核磁共振（NMR）光谱，我们观察到从CHO-K1和MRc40细胞悬液中原位去除甲萘醌的情况。然而，只有在CHO-K1细胞中我们才观察到NMR可见的GSH同时消耗。我们得出结论，GSH代谢的扰动有助于抗性表型，并且是抗甲萘醌CHO细胞的一个重要特征。
Zotero 插件