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1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)、其代谢产物百草枯阳离子(MPP+)与大鼠纹状体和肝脏线粒体中的能量转导

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite cyperquat (MPP+) and energy transduction in mitochondria from rat striatum and liver.

作者信息

Thakar J H, Hassan M N, Grimes J D

机构信息

Parkinson's Disease Laboratory, Ottawa Civic Hospital, Ontario, Canada.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(2-3):355-62. doi: 10.1016/0278-5846(88)90055-3.

Abstract

In vitro studies with rat striatal and liver mitochondria have shown that the neurotoxic compound MPTP (0.5 mM) has very little effect on mitochondrial energy transduction. With pyruvate-malate (P/M), mitochondria from striatum and liver exhibited state 3 oxygen consumption rates of 101.5 +/- 21.3 and 53.6 +/- 14.8, respectively. On the other hand, MPP+ (0.5 mM) inhibited the NAD-linked substrate (P/M) oxidation in both tissue preparations. MPP+ failed to influence oxidative phosphorylation when succinate was used as the substrate. Mitochondria from liver and striatum exhibited low levels of 45Ca uptake in the absence of Mg.ADP. This was increased by about 3-fold in the presence of Mg.ADP. MPP+ under either condition had very little effect on 45Ca uptake by these organelles.

摘要

对大鼠纹状体和肝脏线粒体进行的体外研究表明,神经毒性化合物MPTP(0.5 mM)对线粒体能量转导的影响非常小。使用丙酮酸-苹果酸(P/M)时,纹状体和肝脏的线粒体分别表现出101.5±21.3和53.6±14.8的状态3耗氧率。另一方面,MPP +(0.5 mM)抑制了两种组织制剂中与NAD相关的底物(P/M)氧化。当使用琥珀酸作为底物时,MPP +未能影响氧化磷酸化。在没有Mg.ADP的情况下,肝脏和纹状体的线粒体表现出低水平的45Ca摄取。在存在Mg.ADP的情况下,这增加了约3倍。在任何一种条件下,MPP +对这些细胞器的45Ca摄取影响都非常小。

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