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  • Nicotine And Iron

    From ironjustice@21:1/5 to All on Tue Dec 18 13:16:09 2018
    Nicotine protects against manganese and iron-induced toxicity in SH-SY5Y cells: Implication for Parkinson's disease.
    Neurochem Int. 2018 Dec 14. pii: S0197-0186(18)30592-8.
    doi: 10.1016/j.neuint.2018.12.003.
    Getachew B1, Csoka AB2, Aschner M3, Tizabi Y4.

    Abstract
    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.

    KEYWORDS:
    Cell culture; Iron; Manganese; Neuroprotection; Neurotoxicity; Nicotine; Nicotinic receptors; Parkinson's disease

    PMID: 30557592 DOI: 10.1016/j.neuint.2018.12.003

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