title: GSTpi expression mediates dopaminergic neuron sensitivity in experimental parkinsonism.
abstract: The cause of 95% of Parkinson's disease (PD) cases is unknown. It is hypothesized that PD arises from an interaction of free-radical-generating agents with an underlying genetic susceptibility to these compounds. Here we use the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism to examine the role of a dual function protein, GSTpi, in dopaminergic neuron death. GSTpi is the only GST family member expressed in substantia nigra neurons. GSTpi reduction by pharmacological blockade, RNA inhibition, and gene targeting increases sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, suggesting that differential expression of GSTpi contributes to the sensitivity to xenobiotics in the substantia nigra and may influence the pathogenesis of reactive oxygen species-induced neurological disorders including PD.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Smeyne
authors.forename: Justin
authors.initials: J
authors.lastname: Boyd
authors.forename: Kennie
authors.initials: K
authors.lastname: Raviie Shepherd
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiao
authors.forename: Brooks Barnes
authors.initials: BB
authors.lastname: Pond
authors.forename: Matthew
authors.initials: M
authors.lastname: Hatler
authors.forename: Roland
authors.initials: R
authors.lastname: Wolf
authors.forename: Colin
authors.initials: C
authors.lastname: Henderson
authors.forename: Richard Jay
authors.initials: RJ
authors.lastname: Smeyne
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000201:enzymology* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D015262:Xenobiotics; D051549:Glutathione S-Transferase pi; D004298:Dopamine