1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）、百草枯阳离子（MPP+）和百草枯对大鼠纹状体、皮质和肝脏分离线粒体的影响。

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), cyperquat (MPP+) and paraquat on isolated mitochondria from rat striatum, cortex and liver.

作者信息

Thakar J H, Hassan M N

机构信息

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

出版信息

Life Sci. 1988;43(2):143-9. doi: 10.1016/0024-3205(88)90291-3.

DOI:10.1016/0024-3205(88)90291-3

PMID:3260653

Abstract

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite 1-methyl-4-phenyl pyridinium ion (MPP+, cyperquat) and a structurally-related compound paraquat on mitochondrial functions were investigated in isolated organelles from rat striatum, cortex and liver. MPTP (0.1-1.0 mM) had no significant effect on various parameters of mitochondrial oxidative phosphorylation. In contrast, MPP+ (0.5 mM) inhibited the oxidation of the nicotinamide adenine dinucleotide (NAD+)-linked substrates pyruvate and malate but not that of the flavin adenine dinucleotide (FAD+)-linked substrate succinate. Paraquat (5.0 mM) significantly stimulated basal oxygen consumption (state 4) without influencing the oxygen utilization (state 3) associated with adenosine diphosphate (ADP) phosphorylation. Thus, these structurally-related compounds have different effects on mitochondrial oxidative phosphorylation, but the organelles from striatum, cortex and liver were affected in a similar manner by these compounds.

摘要

研究了1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）、其代谢产物1-甲基-4-苯基吡啶离子（MPP⁺，百草枯阳离子）以及一种结构相关化合物百草枯对大鼠纹状体、皮质和肝脏分离细胞器线粒体功能的影响。MPTP（0.1 - 1.0 mM）对线粒体氧化磷酸化的各项参数无显著影响。相比之下，MPP⁺（0.5 mM）抑制烟酰胺腺嘌呤二核苷酸（NAD⁺）连接底物丙酮酸和苹果酸的氧化，但不抑制黄素腺嘌呤二核苷酸（FAD⁺）连接底物琥珀酸的氧化。百草枯（5.0 mM）显著刺激基础氧消耗（状态4），而不影响与二磷酸腺苷（ADP）磷酸化相关的氧利用（状态3）。因此，这些结构相关化合物对线粒体氧化磷酸化有不同影响，但纹状体、皮质和肝脏的细胞器受这些化合物影响的方式相似。