N-甲基-4-苯基吡啶离子对克隆大鼠嗜铬细胞瘤细胞系PC12h中单胺氧化酶的影响。

Effect of N-methyl-4-phenylpyridinium ion on monoamine oxidase in a clonal rat pheochromocytoma cell line, PC12h.

作者信息

Naoi M, Suzuki H, Kiuchi K, Takahashi T, Nagatsu T

出版信息

J Neurochem. 1987 Jun;48(6):1912-6. doi: 10.1111/j.1471-4159.1987.tb05755.x.

DOI:10.1111/j.1471-4159.1987.tb05755.x

Abstract

The effects of the neurotoxin N-methyl-4-phenylpyridinium ion (MPP+) on the enzymes involved in synthesis and catabolism of catecholamines were examined using a clonal rat pheochromocytoma cell line, PC12h, as a model of dopaminergic neurons. MPP+ added in the culture medium was found to be accumulated in PC12h cells after 30-min incubation. Monoamine oxidase (MAO) activity in PC12h cells was inhibited by MPP+ in a dose-dependent way from 10 nM to 10 microM, but concentrations of MPP+ higher than 100 microM were found to increase the MAO activity. At the lower concentrations MPP+ inhibited MAO noncompetitively with respect to the substrate, kynuramine, and at the higher concentrations it increased both the Km and the Vmax values of MAO toward the substrate. On the other hand, tyrosine hydroxylase activity and the dopamine concentrations in PC12 cells were not changed by incubation with MPP+ for 30 min, 60 min, or 24 h.

摘要

以克隆大鼠嗜铬细胞瘤细胞系PC12h作为多巴胺能神经元模型，研究了神经毒素N-甲基-4-苯基吡啶离子（MPP+）对儿茶酚胺合成和分解代谢相关酶的影响。在培养基中添加MPP+，孵育30分钟后发现其在PC12h细胞中积累。MPP+以剂量依赖方式抑制PC12h细胞中的单胺氧化酶（MAO）活性，浓度范围为10 nM至10 μM，但发现MPP+浓度高于100 μM时会增加MAO活性。在较低浓度下，MPP+对底物犬尿胺非竞争性抑制MAO，而在较高浓度下，它会增加MAO对底物的Km值和Vmax值。另一方面，用MPP+孵育30分钟、60分钟或24小时后，PC12细胞中的酪氨酸羟化酶活性和多巴胺浓度没有变化。