Linked Life Data

17425559

Source:http://linkedlifedata.com/resource/pubmed/id/17425559

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-11
pubmed:abstractText
The survival of injured adult dopaminergic substantia nigra pars compacta neurons can be promoted by various neurotrophic factors. Most neurotrophic factor receptors are activated by intracellular tyrosine phosphorylation upon ligand binding and are subsequently inactivated or dephosphorylated by protein tyrosine phosphatases. This raised the possibility that tyrosine phosphatase inhibition might improve neuronal survival. Here, we infused the stable water-soluble tyrosine phosphatase-specific inhibitor, peroxovanadium [potassium bisperoxo(1,10-phenanthroline)oxovanadate (V) (bpV(phen))], for 14 days close to the substantia nigra starting immediately after a unilateral moderate injury by injection of the neurotoxin 6-hydroxydopamine (6-OHDA) into the midbrain of adult Sprague-Dawley rats. The dopaminergic nigrostriatal neurons were identified by retrograde tracing with fluorogold 7 days prior to the injury. With infusion of 3 or 10 microm peroxovanadium, 75% of these neurons survived compared to 45% in vehicle-infused rats. Degeneration of the dopaminergic projections to the neostriatum was also reduced by 10 microm peroxovanadium. Twenty minutes after an acute injection of peroxovanadium into the substantia nigra, increased tyrosine phosphorylation in Western blots of nigral extracts was seen in the same protein bands as after injections of brain-derived neurotrophic factor (BDNF) or NT-4. This suggests that peroxovanadium enhances endogenous neurotrophic signalling resulting in improved neuronal survival. The neuroprotective effects of this small molecule protein tyrosine phosphatase inhibitor represent a proof-of-principle for a novel treatment strategy in a model for Parkinson's disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1332-40
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17425559-Animals, pubmed-meshheading:17425559-Brain-Derived Neurotrophic Factor, pubmed-meshheading:17425559-Dopamine, pubmed-meshheading:17425559-Dose-Response Relationship, Drug, pubmed-meshheading:17425559-Enzyme Inhibitors, pubmed-meshheading:17425559-Female, pubmed-meshheading:17425559-Gene Expression, pubmed-meshheading:17425559-Nerve Degeneration, pubmed-meshheading:17425559-Nerve Growth Factors, pubmed-meshheading:17425559-Neurons, pubmed-meshheading:17425559-Oxidopamine, pubmed-meshheading:17425559-Phosphorylation, pubmed-meshheading:17425559-Protein Tyrosine Phosphatases, pubmed-meshheading:17425559-Rats, pubmed-meshheading:17425559-Rats, Sprague-Dawley, pubmed-meshheading:17425559-Stilbamidines, pubmed-meshheading:17425559-Substantia Nigra, pubmed-meshheading:17425559-Tyrosine 3-Monooxygenase, pubmed-meshheading:17425559-Vanadates
pubmed:year
2007
pubmed:articleTitle
Protein tyrosine phosphatase inhibition reduces degeneration of dopaminergic substantia nigra neurons and projections in 6-OHDA treated adult rats.
pubmed:affiliation
Kentucky Spinal Cord Injury Research Center and Department of Neurological Surgery, University of Louisville, Louisville, KY 40292, USA. theo.hagg@louisville.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural