Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death

The cause of idiopathic PD is obscure, and most cases are sporadic. Oxidative stress and deficiency of various neurotrophic factors (NTFs) could be factors triggering neurodegeneration in the substantia nigra (SN). Cytoplasmic hybrid cells (cybrids) made from mitochondrial DNA of idiopathic PD subje...

Full description

Bibliographic Details
Main Authors: Isaac G. Onyango, Jeremy B. Tuttle, James P. Bennett, Jr.
Format: Article
Language:English
Published: Elsevier 2005-10-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996105000690
id doaj-d198534db995413ba30df26d4dddf802
record_format Article
spelling doaj-d198534db995413ba30df26d4dddf8022021-03-20T04:51:06ZengElsevierNeurobiology of Disease1095-953X2005-10-01201141154Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal deathIsaac G. Onyango0Jeremy B. Tuttle1James P. Bennett, Jr.2Department of Neuroscience, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA; Department of Neurology, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA; Center for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA; Corresponding authors. I.G. Onyango is to be contacted at Department of Neuroscience, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA. Fax: +1 434 982 4380. J.P. Bennett Jr., Department of Neurology, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA.Department of Neuroscience, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA; Center for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USADepartment of Neurology, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA; Center for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA; Corresponding authors. I.G. Onyango is to be contacted at Department of Neuroscience, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA. Fax: +1 434 982 4380. J.P. Bennett Jr., Department of Neurology, University of Virginia School of Medicine, PO Box 801392, Charlottesville, VA 22908, USA.The cause of idiopathic PD is obscure, and most cases are sporadic. Oxidative stress and deficiency of various neurotrophic factors (NTFs) could be factors triggering neurodegeneration in the substantia nigra (SN). Cytoplasmic hybrid cells (cybrids) made from mitochondrial DNA of idiopathic PD subjects have reduced glutathione (GSH) levels and increased vulnerability to H2O2. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) rescue PD cybrids from H2O2-induced cell death. GDNF mediated effects require Src kinase and phosphatidylinositol 3-kinase (PI3K)/Akt activation. Inhibiting either PI3K/Akt or ERK pathways blocks the effects of BDNF. Inhibiting p38MAPK and c-Jun N-terminal kinase (JNK) pathways enhances the neuroprotective effects of both NTFs. These results demonstrate that expression of PD mitochondrial genes in cybrids increases vulnerability to oxidative stress that is ameliorated by both BDNF and GDNF, which utilize distinct signaling cascades to increase intracellular GSH and enhance survival-promoting cell signaling.http://www.sciencedirect.com/science/article/pii/S0969996105000690Parkinson's diseaseCybridsNeurotrophinsOxidative stressApoptosisMitochondria
collection DOAJ
language English
format Article
sources DOAJ
author Isaac G. Onyango
Jeremy B. Tuttle
James P. Bennett, Jr.
spellingShingle Isaac G. Onyango
Jeremy B. Tuttle
James P. Bennett, Jr.
Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death
Neurobiology of Disease
Parkinson's disease
Cybrids
Neurotrophins
Oxidative stress
Apoptosis
Mitochondria
author_facet Isaac G. Onyango
Jeremy B. Tuttle
James P. Bennett, Jr.
author_sort Isaac G. Onyango
title Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death
title_short Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death
title_full Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death
title_fullStr Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death
title_full_unstemmed Brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect PD cybrids from H2O2-induced neuronal death
title_sort brain-derived growth factor and glial cell line-derived growth factor use distinct intracellular signaling pathways to protect pd cybrids from h2o2-induced neuronal death
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2005-10-01
description The cause of idiopathic PD is obscure, and most cases are sporadic. Oxidative stress and deficiency of various neurotrophic factors (NTFs) could be factors triggering neurodegeneration in the substantia nigra (SN). Cytoplasmic hybrid cells (cybrids) made from mitochondrial DNA of idiopathic PD subjects have reduced glutathione (GSH) levels and increased vulnerability to H2O2. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) rescue PD cybrids from H2O2-induced cell death. GDNF mediated effects require Src kinase and phosphatidylinositol 3-kinase (PI3K)/Akt activation. Inhibiting either PI3K/Akt or ERK pathways blocks the effects of BDNF. Inhibiting p38MAPK and c-Jun N-terminal kinase (JNK) pathways enhances the neuroprotective effects of both NTFs. These results demonstrate that expression of PD mitochondrial genes in cybrids increases vulnerability to oxidative stress that is ameliorated by both BDNF and GDNF, which utilize distinct signaling cascades to increase intracellular GSH and enhance survival-promoting cell signaling.
topic Parkinson's disease
Cybrids
Neurotrophins
Oxidative stress
Apoptosis
Mitochondria
url http://www.sciencedirect.com/science/article/pii/S0969996105000690
work_keys_str_mv AT isaacgonyango brainderivedgrowthfactorandglialcelllinederivedgrowthfactorusedistinctintracellularsignalingpathwaystoprotectpdcybridsfromh2o2inducedneuronaldeath
AT jeremybtuttle brainderivedgrowthfactorandglialcelllinederivedgrowthfactorusedistinctintracellularsignalingpathwaystoprotectpdcybridsfromh2o2inducedneuronaldeath
AT jamespbennettjr brainderivedgrowthfactorandglialcelllinederivedgrowthfactorusedistinctintracellularsignalingpathwaystoprotectpdcybridsfromh2o2inducedneuronaldeath
_version_ 1724212060878798848