MPP(+) 进入小脑颗粒细胞的机制。

Mechanisms of MPP(+) incorporation into cerebellar granule cells.

作者信息

González-Polo R A, Mora A, Clemente N, Sabio G, Centeno F, Soler G, Fuentes J M

机构信息

Depto. Bioquímica y Biología Molecular y Genética, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, Spain.

出版信息

Brain Res Bull. 2001 Sep 15;56(2):119-23. doi: 10.1016/s0361-9230(01)00610-4.

DOI:10.1016/s0361-9230(01)00610-4

PMID:11704348

Abstract

Exposure of cerebellar granule cells to 1-methyl-4-phenylpiridinium (MPP(+)) results in cell death. We have studied the implication of various membrane transporter systems on MPP(+) neurotoxicity, including the dopamine transporter system (DAT) and cationic amino acid transporters (CAT). We have showed a partial protection against MPP(+) toxicity when the dopamine transporter is inhibited by 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]4-(3-phenylpropyl)piperazinedihydrochloride (GBR-12909). However, almost full protection is only achieved by the simultaneous addition of GBR-12909 and cationic amino acids. These results suggest two ways system of MPP(+) entrance into cerebellar granule cells: the DAT with high activity and the CAT with low activity. We also demonstrated that 5,7-dichlorokynurenic acid (MK-801) failed to protect against MPP(+) exposure, evidencing that N-methyl-D-aspartate (NMDA) receptor is not involved in the MPP(+)-induced cell death.

摘要

小脑颗粒细胞暴露于1-甲基-4-苯基吡啶离子（MPP(+)）会导致细胞死亡。我们研究了各种膜转运系统对MPP(+)神经毒性的影响，包括多巴胺转运体系统（DAT）和阳离子氨基酸转运体（CAT）。当多巴胺转运体被1-[2-[双（4-氟苯基）甲氧基]乙基]-4-（3-苯基丙基）哌嗪二盐酸盐（GBR-12909）抑制时，我们已表明对MPP(+)毒性有部分保护作用。然而，只有同时添加GBR-12909和阳离子氨基酸才能实现几乎完全的保护。这些结果表明MPP(+)进入小脑颗粒细胞有两种途径系统：高活性的DAT和低活性的CAT。我们还证明5,7-二氯犬尿氨酸（MK-801）不能保护细胞免受MPP(+)暴露的影响，这表明N-甲基-D-天冬氨酸（NMDA）受体不参与MPP(+)诱导的细胞死亡。