GSTpi expression mediates dopaminergic neuron sensitivity in experimental parkinsonism.
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.
Smeyne
Michelle
M
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Boyd
Justin
J
Raviie Shepherd
Kennie
K
Jiao
Yun
Y
Pond
Brooks Barnes
BB
Hatler
Matthew
M
Wolf
Roland
R
Henderson
Colin
C
Smeyne
Richard Jay
RJ
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
D017382:Reactive Oxygen Species; D015262:Xenobiotics; D051549:Glutathione S-Transferase pi; D004298:Dopamine