Infection with murine retrovirus confers resistance to the neurotoxin 1-methyl-4-phenylpyridinium ion in PC 12 cells.
High concentrations of the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) are toxic to the catecholaminergic cell line PC12, derived from rat phenochromocytoma. Prolonged exposure of wild-type PC12 cells to 500 microM MPP+ yields toxin-resistant colonies at a frequency of 2 X 10(-4). These spontaneously arising MPP(+)-resistant cells are morphologically quite distinct from wild-type PC12 cells, and are lacking in most of their characteristic catecholaminergic properties. In contrast, among PC12 cells infected with the murine retrovirus ZIPNEOSV(X), 20% are resistant to the toxin MPP+, a resistance frequency approximately 1,000 times higher than for uninfected cells. The morphology and catecholaminergic phenotype of the virus-infected MPP+ resistant cells are quite similar to those of wild-type PC12 cells. The results presented in this study suggest a unique mechanism of MPP+ resistance in the infected PC12 cells which may be conferred by the presence and/or expression of the retrovirus ZIPNEOSV(X).
Molecular Biology and Genetics Unit, National Institute on Drug Abuse, Baltimore, Maryland.
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D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001693:Biological Transport, Active; D002470:Cell Survival / Q000187:drug effects; D004093:Dihydropteridine Reductase / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D004351:Drug Resistance; D009693:Nucleic Acid Hybridization; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000378:metabolism; D051381:Rats; D012190:Retroviridae / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D012313:RNA; D014446:Tyrosine 3-Monooxygenase; D004093:Dihydropteridine Reductase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine