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PMID: 1409604 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 19 ·1992-10-01 ·Pages 9074-8

Liu Y, Roghani A, Edwards RH

Abstract

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.

MeSH Terms
1-Methyl-4-phenylpyridinium/pharmacology Animals CHO Cells Cell Survival/drug effects Cricetinae Dopamine/metabolism Dose-Response Relationship, Drug Drug Resistance Kinetics Oxidoreductases/metabolism Oxygen Consumption PC12 Cells Reserpine/pharmacology Rotenone/pharmacology Transfection
Chemicals
Rotenone Reserpine Oxidoreductases 1-Methyl-4-phenylpyridinium Dopamine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Liu Y
Department of Neurology, University of California, Los Angeles School of Medicine 90024-1769.
Roghani A
Edwards R H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.19.9074
Published
1992-10-01
Pages
9074-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50067
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.89.19.9074 PMC Full Text View journal details
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