Journal of Molecular Neuroscience

, Volume 38, Issue 2, pp 114–127 | Cite as

GSTpi Expression in MPTP-Induced Dopaminergic Neurodegeneration of C57BL/6 Mouse Midbrain and Striatum

  • Margarida Castro-Caldas
  • Andreia Neves Carvalho
  • Isabel Peixeiro
  • Elsa Rodrigues
  • Maria Celeste Lechner
  • Maria João Gama
Article

Abstract

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.

Keywords

Glutathione S-transferase pi Parkinson’s disease MPTP Neurodegeneration Detoxification 

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Copyright information

© Humana Press 2008

Authors and Affiliations

  • Margarida Castro-Caldas
    • 1
    • 2
  • Andreia Neves Carvalho
    • 1
  • Isabel Peixeiro
    • 1
  • Elsa Rodrigues
    • 1
  • Maria Celeste Lechner
    • 1
  • Maria João Gama
    • 1
  1. 1.Research Institute for Medicines and Pharmaceutical Sciences—iMED.ULUniversity of LisbonLisbonPortugal
  2. 2.Department of Life Sciences—DCVNew University of Lisbon2829-516 Monte da CaparicaPortugal

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