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

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Oxidopamine
Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositol 3-Kinases
Cell Line
Trypan Blue
Dopaminergic Neurons
Staining and Labeling
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Neurotoxins
Neurodegenerative Diseases
Parkinson Disease
Cell Survival
Cell Count
Cell Membrane

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line : Modulation by inhibitors of PI3 kinase and MEK. / Ugarte, Susana D.; Lin, Eva; Klann, Eric; Zigmond, Michael J.; Perez, Ruth G.

In: Journal of Neuroscience Research, Vol. 73, No. 1, 01.07.2003, p. 105-112.

Research output: Contribution to journalArticle

Ugarte, Susana D. ; Lin, Eva ; Klann, Eric ; Zigmond, Michael J. ; Perez, Ruth G. / Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line : Modulation by inhibitors of PI3 kinase and MEK. In: Journal of Neuroscience Research. 2003 ; Vol. 73, No. 1. pp. 105-112.
@article{a512489417104469b5e22d5b74524665,
title = "Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line: Modulation by inhibitors of PI3 kinase and MEK",
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.",
keywords = "Akt, ERK, MN9D, Oxidative stress, Parkinson's disease",
author = "Ugarte, {Susana D.} and Eva Lin and Eric Klann and Zigmond, {Michael J.} and Perez, {Ruth G.}",
year = "2003",
month = "7",
day = "1",
doi = "10.1002/jnr.10632",
language = "English (US)",
volume = "73",
pages = "105--112",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line

T2 - Modulation by inhibitors of PI3 kinase and MEK

AU - Ugarte, Susana D.

AU - Lin, Eva

AU - Klann, Eric

AU - Zigmond, Michael J.

AU - Perez, Ruth G.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

KW - Akt

KW - ERK

KW - MN9D

KW - Oxidative stress

KW - Parkinson's disease

UR - http://www.scopus.com/inward/record.url?scp=0038054032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038054032&partnerID=8YFLogxK

U2 - 10.1002/jnr.10632

DO - 10.1002/jnr.10632

M3 - Article

VL - 73

SP - 105

EP - 112

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 1

ER -