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Gene transfer of a reserpine-sensitive mechanism of resistance to N-methyl-4-phenylpyridinium.

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PubMed Central1992-10-01 更新2026-05-16 收录
下载链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC50067/
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资源简介:
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. IMAGES:
提供机构:
National Academy of Sciences
创建时间:
1992-10-01
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