Centre for Biomolecular Interactions Bremen, University of Bremen, P.O. Box 330440, D-28334 Bremen, Germany.
Neurochem Int. 2012 Dec;61(8):1302-13. doi: 10.1016/j.neuint.2012.09.007. Epub 2012 Sep 24.
Formaldehyde is a neurotoxic environmental pollutant that can also be produced in the body by certain enzymatic reactions. To test for the potential consequences of an exposure of oligodendrocytes to formaldehyde, we used OLN-93 cells as a model system. Treatment with formaldehyde altered the cellular glutathione (GSH) content of these cells by inducing a rapid time- and concentration-dependent export of GSH. Half-maximal effects were observed for a formaldehyde concentration of about 0.2 mM. While the basal GSH efflux from OLN-93 cells was negligible even when the cellular GSH content was doubled by pre-incubation of the cells with cadmium chloride, the formaldehyde-stimulated export increased almost proportionally to the cellular GSH content. In addition, the stimulated GSH export required the presence of formaldehyde and was almost completely abolished after removal of the aldehyde. Analysis of kinetic parameters of the formaldehyde-induced GSH export revealed similar K(m) and V(max) values of around 100 nmol/mg and 40 nmol/(hmg), respectively, for both OLN-93 cells and cultured astrocytes. The transporter responsible for the formaldehyde-induced GSH export from OLN-93 cells is most likely the multidrug resistance protein 1 (Mrp1), since this transporter is expressed in these cells and since the inhibitor MK571 completely prevented the formaldehyde-induced GSH export. The rapid export of GSH from formaldehyde-treated viable oligodendroglial cells is likely to compromise the cellular antioxidative and detoxification potential which may contribute to the known neurotoxicity of formaldehyde.
甲醛是一种神经毒性的环境污染物，也可以通过某些酶反应在体内产生。为了测试寡突胶质细胞暴露于甲醛的潜在后果，我们使用 OLN-93 细胞作为模型系统。甲醛处理通过诱导 GSH 的快速时间和浓度依赖性外排来改变这些细胞的细胞内谷胱甘肽 (GSH) 含量。观察到半最大效应的甲醛浓度约为 0.2 mM。虽然 OLN-93 细胞的基础 GSH 外流量可以忽略不计，即使通过用氯化镉预孵育细胞将细胞内 GSH 含量增加一倍，甲醛刺激的出口也几乎与细胞内 GSH 含量成比例增加。此外，刺激的 GSH 外排需要甲醛的存在，并且在用醛去除后几乎完全被消除。对甲醛诱导的 GSH 外排的动力学参数进行分析，发现 OLN-93 细胞和培养的星形胶质细胞的类似 K(m)和 V(max)值分别约为 100 nmol/mg 和 40 nmol/(hmg)。负责从 OLN-93 细胞中诱导的 GSH 外排的转运蛋白很可能是多药耐药蛋白 1（Mrp1），因为这种转运蛋白在这些细胞中表达，并且抑制剂 MK571 完全阻止了甲醛诱导的 GSH 外排。从用甲醛处理的存活的少突胶质细胞中快速排出 GSH 可能会损害细胞的抗氧化和解毒潜力，这可能导致甲醛的已知神经毒性。
