Abstract
We previously observed marked down-regulation of the mRNA for angiogenin, a potent inducer of neovascularization, in a mouse model of Parkinson's disease (PD) based on over-expression of alpha-synuclein. Angiogenin has also been recently implicated in the pathogenesis of amyotrophic lateral sclerosis. In this study, we confirmed that mouse angiogenin-1 protein is dramatically reduced in this transgenic alpha-synuclein mouse model of PD, and examined the effect of angiogenin in cellular models of PD. We found that endogenous angiogenin is present in two dopamine-producing neuroblastoma cell lines, SH-SY5Y and M17, and that exogenous angiogenin is taken up by these cells and leads to phosphorylation of Akt. Applied angiogenin protects against the cell death induced by the neurotoxins 1-methyl-4-phenylpyridinium and rotenone and reduces the activation of caspase 3. Together our data supports the importance of angiogenin in protecting against dopaminergic neuronal cell death and suggests its potential as a therapy for PD.
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
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Animals
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Cell Death / drug effects
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Cell Death / physiology
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Cell Line, Tumor
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Cytoprotection / drug effects
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Cytoprotection / physiology
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Disease Models, Animal
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Dopamine / biosynthesis
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Dopamine / physiology
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Humans
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Mice
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Mice, Knockout
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Mice, Transgenic
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Nerve Degeneration / drug therapy
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Nerve Degeneration / genetics
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Nerve Degeneration / prevention & control
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Neuroblastoma / enzymology
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Neuroblastoma / pathology
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Neuroblastoma / therapy
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Neuroprotective Agents / metabolism
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Neuroprotective Agents / pharmacology*
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Oncogene Protein v-akt / metabolism
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / genetics
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Parkinsonian Disorders / metabolism
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Phosphorylation / drug effects
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Phosphorylation / physiology
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Ribonuclease, Pancreatic / metabolism
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Ribonuclease, Pancreatic / pharmacology*
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Ribonuclease, Pancreatic / therapeutic use
Substances
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Neuroprotective Agents
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Oncogene Protein v-akt
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angiogenin
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Ribonuclease, Pancreatic
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Dopamine