GSTpi expression in MPTP-induced dopaminergic neurodegeneration of C57BL/6 mouse midbrain and striatum.
MPTP-induced dopaminergic neurotoxicity involves major biochemical processes such as oxidative stress and impaired energy metabolism, leading to a significant reduction in the number of nigrostriatal dopaminergic neurons. Glutathione S-transferase pi (GSTpi) is a phase II detoxifying enzyme that provides protection of cells from injury by toxic chemicals and products of oxidative stress. In humans, polymorphisms of GSTP1 affect substrate selectivity and stability increasing the susceptibility to parkinsonism-inducing effects of environmental toxins. Given the ability of MPTP to increase the levels of reactive oxygen species and the link between altered redox potential and the expression and activity of GSTpi, we investigated the effect of MPTP on GSTpi cellular concentration in an in vivo model of Parkinson's disease. The present study demonstrates that GSTpi is actively expressed in both substantia nigra pars compacta and striatum of C57BL/6 mice brain, mostly in oligodendrocytes and astrocytes. After systemic administration of MPTP, GSTpi expression is significantly increased in glial cells in the vicinity of dopaminergic neurons cell bodies and fibers. The results suggest that GSTpi expression may be part of the mechanism underlying the ability of glial cells to elicit protection against the mechanisms involved in MPTP-induced neuronal death.
Castro-Caldas
Margarida
M
Research Institute for Medicines and Pharmaceutical Sciences-iMED.UL, University of Lisbon, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
Neves Carvalho
Andreia
A
Peixeiro
Isabel
I
Rodrigues
Elsa
E
Lechner
Maria Celeste
MC
Gama
Maria João
MJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism*; D008636:Mesencephalon / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D015259:Dopamine Agents; D007527:Isoenzymes; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D051549:Glutathione S-Transferase pi; D053148:Caspase 3; D004298:Dopamine
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