MPTP, MPP+ AND MITOCHONDRIAL-FUNCTION
MPTP, MPP+ AND MITOCHONDRIAL-FUNCTION
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DOI：
10.1016/0024-3205(87)90299-2
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发表时间：
1987-02-23
期刊：
影响因子：
6.1
通讯作者：
HEIKKILA, RE
中科院分区：
文献类型：
--
作者：
NICKLAS, WJ;YOUNGSTER, SK;HEIKKILA, RE
神经毒素的有毒代谢产物1-甲基-4-苯基吡啶(MPP+)，1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)可在电子传递系统的络合物I水平上抑制NAD(H)连接的线粒体氧化。MPTP和MPP+抑制小鼠纹状体脑片的有氧糖酵解，通过增加乳酸的产生来衡量；MPTP的诱导作用可以通过抑制单胺氧化酶B的活性来阻止。MPTP的几个神经毒性类似物也通过MAO形成吡啶代谢物；这些MPP+类似物都是NAD(H)连接的线粒体氧化的抑制剂。2‘’-甲基MPTP是一种比MPTP更强的神经毒素，在诱导小鼠脑纹状体脑片乳酸蓄积方面也比MPTP更有效。总体而言，这些研究支持这样的假设，即线粒体氧化能力的损害是MPTP和类似化合物毒性机制中的一个重要因素。
1-Methyl-4-phenylpyridinium (MPP+), the putative toxic metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inhibited NAD(H)-linked mitochondrial oxidation at the level of Complex I of the electron transport system. MPTP and MPP+ inhibited aerobic glycolysis in mouse striatal slices, as measured by increased lactate production; MPTP-induced effects were prevented by inhibition of monoamine oxidase B activity. Several neurotoxic analogs of MPTP also form pyridinium metabolites via MAO; these MPP+ analogs were all inhibitors of NAD(H)-linked oxidation by isolated mitochondria. 2''-Methyl-MPTP, a more potent neurotoxin in mice than MPTP, was also more potent than MPTP in inducing lactate accumulation in mouse brain striatal slices. Overall, the studies support the hypothesis that compromise of mitochondrial oxidative capacity is an important factor in the mechanisms underlying the toxicity of MPTP and similar compounds.