Koehler Yvonne, Luther Eva Maria, Meyer Soeren, Schwerdtle Tanja, Dringen Ralf
Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO Box 330440, D-28334 Bremen, Germany; Centre for Environmental Research and Sustainable Technology, Leobener Strasse, D-28359 Bremen, Germany.
Graduate School of Chemistry, University of Münster, Wilhelm-Klemm-Straße 10, D-48149 Münster, Germany; Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
J Trace Elem Med Biol. 2014 Jul;28(3):328-37. doi: 10.1016/j.jtemb.2014.04.007. Epub 2014 May 4.
Inorganic arsenicals are environmental toxins that have been connected with neuropathies and impaired cognitive functions. To investigate whether such substances accumulate in brain astrocytes and affect their viability and glutathione metabolism, we have exposed cultured primary astrocytes to arsenite or arsenate. Both arsenicals compromised the cell viability of astrocytes in a time- and concentration-dependent manner. However, the early onset of cell toxicity in arsenite-treated astrocytes revealed the higher toxic potential of arsenite compared with arsenate. The concentrations of arsenite and arsenate that caused within 24h half-maximal release of the cytosolic enzyme lactate dehydrogenase were around 0.3mM and 10mM, respectively. The cellular arsenic contents of astrocytes increased rapidly upon exposure to arsenite or arsenate and reached after 4h of incubation almost constant steady state levels. These levels were about 3-times higher in astrocytes that had been exposed to a given concentration of arsenite compared with the respective arsenate condition. Analysis of the intracellular arsenic species revealed that almost exclusively arsenite was present in viable astrocytes that had been exposed to either arsenate or arsenite. The emerging toxicity of arsenite 4h after exposure was accompanied by a loss in cellular total glutathione and by an increase in the cellular glutathione disulfide content. These data suggest that the high arsenite content of astrocytes that had been exposed to inorganic arsenicals causes an increase in the ratio of glutathione disulfide to glutathione which contributes to the toxic potential of these substances.
无机砷化物是与神经病变和认知功能受损相关的环境毒素。为了研究此类物质是否会在脑星形胶质细胞中蓄积并影响其活力及谷胱甘肽代谢，我们将原代培养的星形胶质细胞暴露于亚砷酸盐或砷酸盐中。两种砷化物均以时间和浓度依赖性方式损害星形胶质细胞的活力。然而，亚砷酸盐处理的星形胶质细胞中细胞毒性的早期发作表明，与砷酸盐相比，亚砷酸盐具有更高的毒性潜力。在24小时内导致胞质酶乳酸脱氢酶半数最大释放的亚砷酸盐和砷酸盐浓度分别约为0.3mM和10mM。暴露于亚砷酸盐或砷酸盐后，星形胶质细胞中的细胞砷含量迅速增加，并在孵育4小时后达到几乎恒定的稳态水平。与相应的砷酸盐处理条件相比，暴露于给定浓度亚砷酸盐的星形胶质细胞中的这些水平约高3倍。对细胞内砷形态的分析表明，在暴露于砷酸盐或亚砷酸盐的存活星形胶质细胞中几乎只存在亚砷酸盐。暴露4小时后亚砷酸盐新出现的毒性伴随着细胞总谷胱甘肽的损失和细胞谷胱甘肽二硫化物含量的增加。这些数据表明，暴露于无机砷化物的星形胶质细胞中高含量的亚砷酸盐导致谷胱甘肽二硫化物与谷胱甘肽的比例增加，这促成了这些物质的毒性潜力。
