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首页> 外文期刊>Life sciences >Paradoxical effects of copper and manganese on brain mitochondrial function.
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Paradoxical effects of copper and manganese on brain mitochondrial function.

机译：铜和锰对脑线粒体功能的悖论作用。

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Defects in the mitochondrial genome have been associated with Parkinson's and Alzheimer's disease, and apoptosis can be triggered by the presence of energetically compromised mitochondria. Thus, in this study we have examined whether the divalent cations Cu2+ and Mn2+ could influence mitochondrial function in vitro. Mitochondrial electron transport was dose and time dependently reduced by Cu2+ to a greater extent with succinate as a substrate. Following a 60 min preincubation period, Mn2+ dose dependently inhibited electron transport to a greater extent with lactate and malate. In contrast, paradoxical effects were seen following a 5 min preincubation period with Mn2+. Cu2+ dose-dependently reduced NADH-dependent lactate dehydrogenase (LDH) activity, with almost complete inhibition apparent at 10 microM. An initial induction of LDH by 10 microM Mn2+ was partially reversed by higher concentrations of the metal. Cu2+ dose-dependently reduced flavin adenine dinucleotide (FAD)-dependent monoamine oxidase A (MAO-A) activity in a time-independent manner, with an IC50 value approximately 20 microM, whereas Mn2+ had no effect. In conclusion, it is proposed that Cu2+ and Mn2+ have differential effects on nicotinamide adenine dinucleotide (NAD) and FAD-dependent mitochondrial enzymes at the level of the essential cofactors. Cu2+ appears to exert an inhibitory effect on both NAD and FAD-dependent enzymes, but predominantly against the latter, including MAO-A and succinate dehydrogenase. The complex responses to Mn2+ may be due to dose-related effects on the interconversion of NAD and NADH and reversible enzymatic reactions employing this nucleotide cofactor.
机译：线粒体基因组的缺陷与帕金森氏病和阿尔茨海默氏病有关，细胞凋亡可通过能量受损的线粒体的存在而触发。因此，在这项研究中，我们研究了二价阳离子Cu2 +和Mn2 +是否可以在体外影响线粒体功能。以琥珀酸酯为底物，线粒体电子传递的剂量和时间依赖性地被Cu2 +降低到更大的程度。经过60分钟的预温育期，Mn2 +剂量在较大程度上抑制了乳酸和苹果酸的电子传输。相反，在与Mn2 +一起孵育5分钟后，看到了自相矛盾的效应。 Cu 2+剂量依赖性地降低了NADH依赖性乳酸脱氢酶（LDH）的活性，在10 microM时几乎完全抑制。 10 microM Mn2 +对LDH的初始诱导被较高浓度的金属部分逆转。 Cu2 +以时间依赖性方式降低了黄素腺嘌呤二核苷酸（FAD）依赖性单胺氧化酶A（MAO-A）的活性，其IC50值约为20 microM，而Mn2 +没有作用。总之，有人提出，Cu2 +和Mn2 +在基本辅因子水平上对烟酰胺腺嘌呤二核苷酸（NAD）和FAD依赖的线粒体酶具有不同的作用。 Cu 2+似乎对NAD和FAD依赖性酶均具有抑制作用，但主要针对后者，包括MAO-A和琥珀酸脱氢酶。对Mn2 +的复杂反应可能是由于剂量相关的对NAD和NADH相互转化的影响以及采用该核苷酸辅因子的可逆酶促反应。

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