Manganese-induced neurotoxicity is differentially enhanced by glutathione depletion in astrocytoma and neuroblastoma cells
Manganese-induced neurotoxicity is differentially enhanced by glutathione depletion in astrocytoma and neuroblastoma cells
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DOI：
10.1007/s11064-006-9179-7
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发表时间：
2006-11-01
影响因子：
4.4
通讯作者：
Lai, James C. K.
中科院分区：
文献类型：
--
作者：
Dukhande, Vikas V.;Malthankar-Phatak, Gauri H.;Lai, James C. K.
锰（Mn）具有神经毒性：其潜在机制尚未完全阐明。L-丁硫氨酸-（S，R）-亚砜亚胺（BSO）是谷氨酰半胱氨酸合成酶的不可逆抑制剂，谷氨酰半胱氨酸合成酶是谷胱甘肽（GSH）合成的重要酶。为了检验BSO调节Mn毒性的假设，我们研究了用MnCl 2、BSO或MnCl 2加BSO处理U-87或SK-N-SH细胞的效果。我们使用MTT测定法监测细胞活力，用HO-33342染色以评估活细胞和/或凋亡细胞，并用碘化丙啶（PI）染色以评估坏死细胞;我们还测量了细胞谷胱甘肽。我们的研究结果表明，当用MnCl 2或BSO处理时，两种细胞类型的活力降低：Mn对SK-N-SH细胞更具毒性，而BSO对U-87细胞更具毒性。由于BSO治疗加重锰毒性在两个细胞系中，谷胱甘肽可能会采取行动，以打击锰毒性。因此，进一步研究谷胱甘肽耗竭介导的氧化应激将揭示新的Mn毒性机制。
Manganese (Mn) is neurotoxic: the underlying mechanisms have not been fully elucidated. L-Buthionine-(S,R)-sulfoximine (BSO) is an irreversible inhibitor of gamma-glutamylcysteine synthetase, an important enzyme in glutathione (GSH) synthesis. To test the hypothesis that BSO modulates Mn toxicity, we investigated the effects of treatment of U-87 or SK-N-SH cells with MnCl2, BSO, or MnCl2 plus BSO. We monitored cell viability using MTT assay, staining with HO-33342 to assess live and/or apoptotic cells, and staining with propidium iodide (PI) to assess necrotic cells; we also measured cellular glutathione. Our results indicate decreased viability in both cell types when treated with MnCl2 or BSO: Mn was more toxic to SK-N-SH cells, whereas BSO was more toxic to U-87 cells. Because BSO treatment accentuated Mn toxicity in both cell lines, GSH may act to combat Mn toxicity. Thus, further investigation in oxidative stress mediated by glutathione depletion will unravel new Mn toxicity mechanism(s).