Leung T K, Lim L, Lai J C
Department of Neurochemistry, University of London, Queen Square, U.K.
Metab Brain Dis. 1992 Sep;7(3):139-46. doi: 10.1007/BF01000159.
To investigate the hypothesis that neurotoxic metals can exert their toxicity through the direct inhibition of monoamine oxidases (MAOs), the effects of several neurotoxic metal ions on type A (MAO-A) and type B (MAO-B) monoamine oxidase activities in rat forebrain nonsynaptic mitochondria and rat liver mitochondria were studied. At pathophysiological levels (10-100 microM), Cu2+ and Cd2+ are good inhibitors of brain mitochondrial MAO-A and, to a lesser extent, liver mitochondrial MAO-A. The inhibition of MAO-B activities in brain and liver mitochondria by Cu2+ and Cd2+ is only detected at the higher end of the concentration range (i.e., 50-100 microM). At the pathophysiological level of 0.5 mM, Al3+ only inhibits brain mitochondrial MAO-A but at the higher level of 2.5 mM, it inhibits both forms of MAO in brain as well as liver mitochondria. Even at toxic levels (e.g., 5 mM), neither Mn2+ nor Li+ inhibits the activities of MAO-A and MAO-B in brain and liver mitochondria. Our results are consistent with the hypothesis that some neurotoxic metals can exert their toxicity through the direct inhibition of the isoforms of MAO. Our data also suggest that the selective inhibition of brain MAO-A by Cu2+ and Cd2+ may assume pathophysiological importance in the neurotoxicity of copper and cadmium.
为了研究神经毒性金属可通过直接抑制单胺氧化酶（MAOs）发挥毒性这一假说，我们研究了几种神经毒性金属离子对大鼠前脑非突触线粒体和大鼠肝脏线粒体中A型（MAO - A）和B型（MAO - B）单胺氧化酶活性的影响。在病理生理水平（10 - 100微摩尔），Cu2+和Cd2+是脑线粒体MAO - A的良好抑制剂，对肝脏线粒体MAO - A的抑制作用较小。仅在浓度范围较高端（即50 - 100微摩尔）才检测到Cu2+和Cd2+对脑和肝脏线粒体中MAO - B活性的抑制作用。在0.5毫摩尔的病理生理水平下，Al3+仅抑制脑线粒体MAO - A，但在2.5毫摩尔的较高水平时，它会抑制脑和肝脏线粒体中的两种MAO形式。即使在毒性水平（例如5毫摩尔），Mn2+和Li+也不会抑制脑和肝脏线粒体中MAO - A和MAO - B的活性。我们的结果与某些神经毒性金属可通过直接抑制MAO同工型发挥毒性这一假说一致。我们的数据还表明，Cu2+和Cd2+对脑MAO - A的选择性抑制可能在铜和镉的神经毒性中具有病理生理重要性。
