PMID- 17425559
OWN - NLM
STAT- MEDLINE
DCOM- 20070625
LR  - 20161124
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 25
IP  - 5
DP  - 2007 Mar
TI  - Protein tyrosine phosphatase inhibition reduces degeneration of dopaminergic 
      substantia nigra neurons and projections in 6-OHDA treated adult rats.
PG  - 1332-40
AB  - 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.
FAU - Yang, Peng
AU  - Yang P
AD  - Kentucky Spinal Cord Injury Research Center and Department of Neurological 
      Surgery, University of Louisville, Louisville, KY 40292, USA. 
      theo.hagg@louisville.edu
FAU - Dankowski, Aygul
AU  - Dankowski A
FAU - Hagg, Theo
AU  - Hagg T
LA  - eng
GR  - NS 44706/NS/NINDS NIH HHS/United States
GR  - RR 15576/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Stilbamidines)
RN  - 3WHH0066W5 (Vanadates)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - P658DCA9XD (neurotrophin 4)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dopamine/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Female
MH  - Gene Expression/drug effects
MH  - Nerve Degeneration/chemically induced/*drug therapy
MH  - Nerve Growth Factors/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Oxidopamine
MH  - Phosphorylation/drug effects
MH  - Protein Tyrosine Phosphatases/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stilbamidines/metabolism
MH  - Substantia Nigra/*cytology
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Vanadates/therapeutic use
EDAT- 2007/04/12 09:00
MHDA- 2007/06/26 09:00
CRDT- 2007/04/12 09:00
PHST- 2007/04/12 09:00 [pubmed]
PHST- 2007/06/26 09:00 [medline]
PHST- 2007/04/12 09:00 [entrez]
AID - EJN5384 [pii]
AID - 10.1111/j.1460-9568.2007.05384.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2007 Mar;25(5):1332-40. doi: 10.1111/j.1460-9568.2007.05384.x.