Linked Life Data

16086684

Source:http://linkedlifedata.com/resource/pubmed/id/16086684

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-9-29
pubmed:abstractText
High-dose methamphetamine (METH) is associated with long-term deficits in dopaminergic systems. Although the mechanism(s) which contributes to these deficits is not known, glutamate and peroxynitrite are likely to play a role. These factors are hypothesized to inhibit mitochondrial function, increasing the free radical burden and decreasing neuronal energy supplies. Previous studies suggest a role for the mitochondrial electron transport chain (ETC) in mediating toxicity of METH. The purpose of the present studies was to determine whether METH administration selectively inhibits complex II of the ETC in rats. High-dose METH administration (10 mg/kg every 2 h x 4) rapidly (within 1 h) decreased complex II (succinate dehydrogenase) activity by approximately 20-30%. In addition, decreased activity of complex II-III, but not complex I-III, of the mitochondrial ETC was also observed 24 h after METH. This inhibition was not due to direct inhibition by METH or METH-induced hyperthermia and was specific to striatal brain regions. METH-induced decreases in complex II-III were prevented by MK-801 and the peroxynitrite scavenger 5,10,15,20-tetrakis (2,4,6-trimethyl-3,5-sulphonatophenyl) porphinato iron III. These findings provide the first evidence that METH administration, via glutamate receptor activation and peroxynitrite formation, selectively alters a specific site of the ETC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
429-36
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16086684-Animals, pubmed-meshheading:16086684-Central Nervous System Stimulants, pubmed-meshheading:16086684-Dose-Response Relationship, Drug, pubmed-meshheading:16086684-Electron Transport, pubmed-meshheading:16086684-Electron Transport Complex II, pubmed-meshheading:16086684-Enzyme Activation, pubmed-meshheading:16086684-Excitatory Amino Acid Antagonists, pubmed-meshheading:16086684-Glutamic Acid, pubmed-meshheading:16086684-Male, pubmed-meshheading:16086684-Methamphetamine, pubmed-meshheading:16086684-Mitochondria, pubmed-meshheading:16086684-Nitric Oxide Synthase, pubmed-meshheading:16086684-Peroxynitrous Acid, pubmed-meshheading:16086684-Rats, pubmed-meshheading:16086684-Rats, Sprague-Dawley, pubmed-meshheading:16086684-Receptors, Glutamate, pubmed-meshheading:16086684-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:16086684-Succinate Dehydrogenase
pubmed:year
2005
pubmed:articleTitle
Methamphetamine-induced inhibition of mitochondrial complex II: roles of glutamate and peroxynitrite.
pubmed:affiliation
Department of Pharmacology and Experimental Therapeutics, Laboratory of Neurochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural