Caito Samuel W, Aschner Michael
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461
Toxicol Sci. 2016 May;151(1):139-49. doi: 10.1093/toxsci/kfw030. Epub 2016 Feb 10.
Methylmercury (MeHg) is a neurotoxic contaminant of our fish supply that has been linked to dopaminergic (DAergic) dysfunction that characterizes Parkinson's disease. We have previously shown that MeHg causes both morphological and behavioral changes in the Caenorhabditis elegans DAergic neurons that are associated with oxidative stress. We were therefore interested in whether the redox sensitive cofactor nicotinamide adenine dinucleotide (NAD(+)) may be affected by MeHg and whether supplementation of NAD( + )may prevent MeHg-induced toxicities. Worms treated with MeHg showed depletion in cellular NAD( + )levels, which was prevented by NAD( + )supplementation prior to MeHg treatment. NAD( + )supplementation also prevented DAergic neurodegeneration and deficits in DAergic-dependent behavior upon MeHg exposure. In a mutant worm line that cannot synthesize NAD( + )from nicotinamide, MeHg lethality and DAergic behavioral deficits were more sensitive to MeHg than wildtype worms, demonstrating the importance of NAD( + )in MeHg toxicity. In wildtype worms, NAD( + )supplementation provided protection from MeHg-induced oxidative stress and mitochondrial dysfunction. These data show the importance of NAD( + )levels in the response to MeHg exposure. NAD( + )supplementation may be beneficial for MeHg-induced toxicities and preventing cellular damage involved in Parkinson's disease.
甲基汞（MeHg）是我们鱼类供应中的一种神经毒性污染物，它与帕金森病所特有的多巴胺能（DAergic）功能障碍有关。我们之前已经表明，MeHg会导致秀丽隐杆线虫多巴胺能神经元出现形态和行为变化，这些变化与氧化应激相关。因此，我们感兴趣的是，氧化还原敏感辅因子烟酰胺腺嘌呤二核苷酸（NAD(+)）是否会受到MeHg的影响，以及补充NAD(+)是否可以预防MeHg诱导的毒性。用MeHg处理的线虫显示细胞内NAD(+)水平降低，而在MeHg处理前补充NAD(+)可预防这种情况。补充NAD(+)还可预防MeHg暴露后多巴胺能神经变性以及多巴胺能依赖性行为缺陷。在一种无法从烟酰胺合成NAD(+)的突变线虫品系中，MeHg致死率和多巴胺能行为缺陷比野生型线虫对MeHg更敏感，这表明NAD(+)在MeHg毒性中的重要性。在野生型线虫中，补充NAD(+)可保护其免受MeHg诱导的氧化应激和线粒体功能障碍。这些数据表明NAD(+)水平在应对MeHg暴露中的重要性。补充NAD(+)可能对MeHg诱导的毒性以及预防帕金森病中涉及的细胞损伤有益。
