Linked Life Data

3498818

Source:http://linkedlifedata.com/resource/pubmed/id/3498818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1987-11-5
pubmed:abstractText
In previous studies and in the accompanying paper, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP) was found to be more potent than MPTP in producing dopaminergic neurotoxicity in mice. One purpose of the present study was to determine whether 1-methyl-4-(2'-methylphenyl)pyridinium (2'CH3-MPP+), the primary oxidation product of 2'CH3-MPTP both in vivo and in vitro, inhibits mitochondrial respiration as does 1-methyl-4-phenylpyridinium (MPP+), the primary oxidation product of MPTP. Another aim was to determine whether treatments which modify MPTP- and 2'CH3-MPTP-induced neurotoxicity in vivo also cause parallel changes in the metabolic toxicity of these compounds. It was found that 2'CH3-MPP+, like MPP+, inhibited the oxidation of NAD(H)-linked substrates by isolated brain mitochondria in a concentration- and time-dependent manner, whereas succinate oxidation was not affected. Thus, the effect was on Complex I in the electron transport chain. Furthermore, 2'CH3-MPP+, like MPP+, enhanced lactate formation by neostriatal tissue slices as would be expected if Complex respiration were inhibited. MPP+ was slightly more potent than 2'CH3-MPP+ in both of these studies. However, 2'CH3-MPTP was several-fold more potent than MPTP in increasing lactate accumulation by the neostriatal slices. This difference in potency correlated with the differing capacities of 2'CH3-MPTP and MPTP to be oxidized by monoamine oxidase (MAO).(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
242
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
858-63
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Mitochondrial and metabolic toxicity of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine.
pubmed:affiliation
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't