Linked Life Data

17017526

Source:http://linkedlifedata.com/resource/pubmed/id/17017526

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
70
pubmed:dateCreated
2006-10-4
pubmed:abstractText
Elucidation of the biochemical steps leading to the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-induced degeneration of the nigro-striatal dopamine (DA) pathway has provided new clues to the pathophysiology of Parkinson's Disease (PD). In line with the enhancement of MPTP toxicity by diethyldithiocarbamate (DDC), here we demonstrate how other CYP450 (2E1) inhibitors, such as diallyl sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective DA neuron degeneration in C57/bl mice. In order to provide direct evidence for this isozyme involvement, CYP 2E1 knockout mice were challenged with MPTP or the combined treatment. Here we show that these transgenic mice have a low sensitivity to MPTP alone, similarly to the wild type SVI, suggesting that it is likely that transgenic mice compensate for the missing enzyme. However, in these CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP toxicity; this enhancement is instead regularly present in the SVI control animals. This study indicates that the occurrence of CYP 2E1 in C57/bl mouse brain is relevant for MPTP toxicity, and suggests that this isozyme may have a detoxificant role related to the efflux transporter of the toxin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0303-6995
pubmed:author
pubmed:issnType
Print
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-6
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Cytochrome P450 and Parkinson's disease: protective role of neuronal CYP 2E1 from MPTP toxicity.
pubmed:affiliation
Department of Neuroscience, Section of Pharmacology, University of Pisa, Italy.
pubmed:publicationType
Journal Article