Energy-driven uptake of N-methyl-4-phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP.
Energy-driven uptake of N-methyl-4-phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP.
复制标题
脑线粒体能量驱动的 N-甲基-4-苯基吡啶摄取介导 MPTP 的神经毒性。
DOI：
10.1016/0024-3205(86)90037-8
复制
发表时间：
1986
期刊：
影响因子：
6.1
通讯作者：
Singer,TP
中科院分区：
文献类型：
--
作者：
Ramsay,RR;Dadgar,J;Trevor,A;Singer,TP
0.5 mM N-甲基-4-苯基吡啶(MPP+)可完全抑制大鼠脑线粒体对NAD+连接底物的氧化。这种作用取决于线粒体的完整性，因为需要更高浓度的MPP+来抑制倒置线粒体或分离的内膜制剂中的NADH氧化。这种行为差异的原因被追溯到一种新的系统，即反浓度梯度地将MPP+摄取到线粒体中。摄取系统由跨膜电位提供能量，这一事实表明，瓦林霉素加K+消除了这种梯度，取消了MPP+的摄取，而消除质子梯度的试剂对这一过程没有影响。如果在预先负载MPP+的线粒体中加入解偶联剂，则后者的外流会随着浓度的升高而发生。已经在大鼠的肝脏、全脑、皮质和中脑标本中研究了摄取系统。它可能很容易与突触多巴胺再摄取系统区分开来，因为前者被解偶联剂和呼吸抑制剂阻断，但不被多巴胺或马吲哚阻断，而突触系统被马吲哚阻断，并被多巴胺竞争性抑制，但不受呼吸抑制剂或解偶联剂的影响。脑线粒体对MPP+的能量驱动摄取可能是导致其前体MPTP神经毒性作用的复杂事件序列中的关键一步。
The oxidation of NAD+-linked substrates by rat brain mitochondria is completely inhibited by pre-incubation with 0.5 mM N-methyl-4-phenylpyridine (MPP+). The effect is dependent on the integrity of the mitochondria because far higher concentrations of MPP+are required to inhibit NADH oxidation in inverted mitochondria or isolated inner membrane preparations. The reason for this difference in behavior has been traced to a novel system for the uptake of MPP+into mitochondria against a concentration gradient. The uptake system is energized by the transmembrane potential, as shown by the fact that valinomycin plus K+, which collapses this gradient, abolishes MPP+uptake, while agents which collapse the proton gradient have no effect on the process. If an uncoupler is added to mitochondria preloaded with MPP+, efflux of the latter occurs with the concentration gradient. The uptake system has been studied in liver, whole brain, cortex, and midbrain preparations from rats. It may be readily distinguished from the synaptic dopamine reuptake system, since the former is blocked by uncouplers and respiratory inhibitors, but not by dopamine or mazindol, whereas the synaptic system is blocked by mazindol and competitively inhibited by dopamine but is not affected by respiratory inhibitors or uncouplers. Energy-driven uptake of MPP+by brain mitochondria may be a crucial step in the complex sequence of events leading to the neurotoxic actions of its precursor, MPTP.
登录
查看更多内容
肝匀浆组分对黑质纹状体毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶的代谢。
影响因子：
7.3
作者：
Weissman,J;Trevor,A;Chiba,K;Peterson,LA;Caldera,P;CastagnoliJr,N;Baillie,T
通讯作者：
Baillie,T
单胺氧化酶 A 和 B 氧化神经毒性胺 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)，并通过 MPTP 自杀灭活酶。
DOI：
10.1016/0006-291x(84)90614-4
发表时间：
1984
影响因子：
3.1
作者：
Salach,JI;Singer,TP;CastagnoliJr,N;Trevor,A
通讯作者：
Trevor,A
电子顺磁共振波谱法研究还原型二磷酸吡啶核苷酸脱氢酶的动力学
影响因子：
4.8
作者：
H. Beinert;H. Beinert;G. Palmer;G. Palmer;T. Cremona;T. Cremona;T. Singer;T. Singer
通讯作者：
T. Singer
1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 对单胺氧化酶的可逆抑制和基于机制的不可逆失活。
DOI：
10.1016/s0006-291x(85)80219-9
发表时间：
1985
影响因子：
3.1
作者：
T. Singer;J. Salach;D. Crabtree
通讯作者：
D. Crabtree
DOI：
10.1016/0006-3002(56)90058-0
发表时间：
1956-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CRANE, FL;GLENN, JL;GREEN, DE
通讯作者：
GREEN, DE