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...
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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 |
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