Manganese (Mn) and iron (Fe) are trace elements that are essential for proper growth and physiological functions as both play critical role in a variety of enzymatic reactions. At high concentrations, however, they can be toxic and cause neurodegenerative disorders, particularly Parkinson-like syndromes. Nicotine, on the other hand, has been shown to have neuroprotective effects against various endogenous or exogenous toxins that selectively damage the dopaminergic cells. These cells include neuroblastoma-derived SH-SY5Y cells which express significant dopaminergic activity. However, practically no information on possible neuroprotective effects of nicotine against toxicity induced by trace elements is available. Therefore, in this study we investigated the effects of nicotine on toxicity induced by manganese or iron in these cells. Exposure of SH-SY5Y cells for 24 h to manganese (20 μM) or iron (20 μM) resulted in approximately 30% and 35% toxicity, respectively. Pretreatment with nicotine (1 μM) completely blocked the toxicities of Mn and Fe. The effects of nicotine, in turn, were blocked by selective nicotinic receptor antagonists. Thus, dihydro-beta erythroidine (DHBE), a selective alpha 4-beta 2 subtype antagonist and methyllycaconitine (MLA), a selective alpha7 antagonist, as well as mecamylamine, a non-selective nicotinic antagonist all dose-dependently blocked the protective effects of nicotine against both Mn and Fe. These findings provide further support for the potential utility of nicotine or nicotinic agonists in Parkinson's disease-like neurodegenerative disorders, including those that might be precipitated by trace elements, such as Fe and Mn. Moreover, both alpha4-beta2 and alpha7 nicotinic receptor subtypes appear to mediate the neuroprotective effects of nicotine against toxicity induced by these two trace metals.

中文翻译：

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尼古丁可防止 SH-SY5Y 细胞中锰和铁诱导的毒性：对帕金森病的影响。


锰 (Mn) 和铁 (Fe) 是正常生长和生理功能所必需的微量元素，因为它们在各种酶反应中都发挥着关键作用。然而，在高浓度下，它们可能有毒并导致神经退行性疾病，特别是帕金森样综合征。另一方面，尼古丁已被证明对选择性损害多巴胺能细胞的各种内源性或外源性毒素具有神经保护作用。这些细胞包括神经母细胞瘤衍生的 SH-SY5Y 细胞，其表达显着的多巴胺能活性。然而，实际上没有关于尼古丁对微量元素引起的毒性可能的神经保护作用的信息。因此，在这项研究中，我们研究了尼古丁对锰或铁在这些细胞中诱导的毒性的影响。 SH-SY5Y 细胞暴露于锰 (20 μM) 或铁 (20 μM) 24 小时，分别导致约 30% 和 35% 的毒性。用尼古丁 (1 μM) 预处理完全阻断了 Mn 和 Fe 的毒性。尼古丁的作用反过来又被选择性烟碱受体拮抗剂阻断。因此，二氢-β赤霉素（DHBE）（一种选择性α4-β2亚型拮抗剂）和甲基乌头碱（MLA）（一种选择性α7拮抗剂）以及美加明（一种非选择性烟碱拮抗剂）均剂量依赖性地阻断了尼古丁对 Mn 和 Fe 都有作用。这些发现进一步支持了尼古丁或烟碱激动剂在帕金森病样神经退行性疾病中的潜在用途，包括那些可能由微量元素（如铁和锰）诱发的神经退行性疾病。 此外，α4-β2 和 α7 烟碱受体亚型似乎都能介导尼古丁对这两种微量金属引起的毒性的神经保护作用。