Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line: Modulation by inhibitors of PI3 kinase and MEK

Susana D. Ugarte, Eva Lin, Eric Klann, Michael J. Zigmond, Ruth G. Perez

Research output: Contribution to journalArticle

Abstract

Parkinson's disease is a neurodegenerative disorder associated with the selective death of dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF) can protect dopaminergic neurons in several parkinsonian models. We used the dopaminergic cell line MN9D to explore the mechanisms underlying GDNF-mediated protection against the neurotoxin 6-hydroxydopamine (6-OHDA). MN9D cell viability was decreased 24 hr after a 15-min exposure to 6-OHDA (50-1,000 μM) as revealed by staining with Hoechst reagent and Trypan blue. The addition of GDNF (10 ng/ml) before, during, and after exposure to 6-OHDA significantly increased the number of viable cells as assessed by Hoechst staining. In contrast, 6-OHDA-induced cell membrane damage was unaffected as measured by Trypan blue exclusion. The PI3K specific inhibitor LY294002 (10-50 μM) blocked GDNF-mediated protection against nuclear condensation, as did the MAPK kinase (MEK) inhibitor U0126 (5-20 μM). These studies suggest that GDNF can protect dopaminergic cells against some but not all aspects of 6-OHDA-induced toxicity by acting through both PI3K and MAPK signaling pathways.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalJournal of neuroscience research
Volume73
Issue number1
DOIs
StatePublished - Jul 1 2003

Keywords

  • Akt
  • ERK
  • MN9D
  • Oxidative stress
  • Parkinson's disease

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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