Organ-specific manganese toxicity:: a comparative in vitro study on five cellular models exposed to MnCl2
Organ-specific manganese toxicity:: a comparative in vitro study on five cellular models exposed to MnCl2
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DOI：
10.1016/j.tiv.2006.08.010
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发表时间：
2007-03-01
影响因子：
3.2
通讯作者：
Mazzoleni, G.
中科院分区：
文献类型：
--
作者：
Rovetta, F.;Catalani, S.;Mazzoleni, G.
锰（Mn）既是一种必需营养素，也是一种有毒物质，对肝脏和肾脏（急性接触）以及中枢神经系统（CNS）（慢性接触）有特定影响。锰神经毒性包括神经行为障碍和锥体外系运动功能障碍（锰中毒），可能是由于基底神经节局灶性损伤所致。即使广泛调查，负责锰毒性的分子机制仍有待澄清。本研究的目的是确定合适的体外模型来研究这些分子途径。为此，我们比较了氯化锰对四种细胞系的影响，这些细胞系代表了体内锰毒性的主要靶器官。分别选择HepG 2和MDCK细胞系用于肝脏和肾脏;神经胶质细胞GL 15和神经元SHSY 5 Y细胞用作CNS组分的模型。为了完成“运动系统”模型，还包括骨骼肌C2Cl 2细胞。我们的研究结果表明，肝，肾，神经胶质细胞和神经元细胞类型不同的反应锰，反映了特定的体内反应的组织，他们代表。这证实了它们作为研究Mn相关毒性事件的合适体外模型的价值。有趣的是，肌肉C2Cl 2细胞也显示出对Mn的明显敏感性，优先靶点是分化的肌管。(c)2006爱思唯尔有限公司保留所有权利。
Manganese (Mn) is both an essential nutrient and a toxicant, with specific effects on liver and kidney (acute exposure) and on central nervous system (CNS) (chronic exposure). Mn neurotoxicity includes neurobehavioral disorders and extra-pyramidal motor dysfunctions (manganism), possibly due to focal injuries to the basal ganglia. Even if widely investigated, the molecular mechanisms responsible for Mn toxicity remain to be clarified. Aim of this study was to identify suitable in vitro models to investigate these molecular pathways. To this purpose we compared the effect of manganese chloride on four cell lines, representative of the main target organs of Mn toxicity in vivo. HepG2 and MDCK cell lines were selected for liver and kidney, respectively; glial GL15 and neuronal SHSY5Y cells were used as models of CNS components. To complete the "motor system" model, skeletal muscle C2Cl2 cells were also included. Our results demonstrate that hepatic, renal, glial and neuronal cell types differently react to Mn, mirroring the specific in vivo response of the tissue they represent. This confirms their value as suitable in vitro models to study Mn-related toxic events. Interestingly, also muscle C2Cl2 cells showed a noticeable sensitivity to Mn, preferential targets being differentiated myotubes. (c) 2006 Elsevier Ltd. All rights reserved.