GENE-TRANSFER OF A RESERPINE-SENSITIVE MECHANISM OF RESISTANCE TO N-METHYL-4-PHENYLPYRIDINIUM

被引：111

作者：

LIU, Y ^{[1
]}

ROGHANI, A ^{[1
]}

EDWARDS, RH ^{[1
]}

机构：

[1] UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, 710 WESTWOOD PLAZA, LOS ANGELES, CA 90024 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1992年 / 89卷 / 19期

关键词：

VESICULAR AMINE TRANSPORTER; PARKINSON DISEASE;

D O I：

10.1073/pnas.89.19.9074

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The toxin N-methyl-1,2,3,6-tetrahydropyridine produces a model of neural degeneration very similar to idiopathic Parkinson disease. To understand the cellular mechanisms that modulate susceptibility to its active metabolite N-methyl-4-phenylpyridinium (MPP+), we have transfected a cDNA expression library from the relatively MPP+-resistant rat pheochromocytoma PC12 cells into MPP+-sensitive Chinese hamster ovary (CHO) fibroblasts. Selection of the stable transformants in high concentrations of MPP+ has yielded a clone extremely resistant to the toxin. Reserpine reverses the resistance to MPP+, suggesting that a transport activity protects against this form of toxicity, perhaps by sequestering the toxin within an intracellular compartment. In support of this hypothesis, dopamine loaded into the CHO transformant shows a localized distribution that is distinct from the pattern observed in wild-type cells and is also reversed by reserpine.

引用

页码：9074 / 9078

页数：5

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