Linked Life Data

11597127

Source:http://linkedlifedata.com/resource/pubmed/id/11597127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-10-12
pubmed:abstractText
Treatment of U937 cells with nontoxic concentrations of TNFalpha increased the DNA strand scission induced by a short-chain lipid hydroperoxide analogue, tert-butylhydroperoxide. The following lines of evidence suggest that the enhancing effects of TNFalpha are mediated by inhibition of complex III and by the ensuing formation of superoxides and hydrogen peroxide: (a) the effects of TNFalpha were mimicked by the complex III inhibitor antimycin A; (b) the effects of TNFalpha, or antimycin A, were abolished by the complex I inhibitor rotenone, or by myxothiazol, an agent which inhibits the electron flow from the reduced coenzyme Q to cytochrome c(1) and therefore prevents ubisemiquinone formation; (c) the effects of TNFalpha, or antimycin A, were not observed in respiration-deficient cells; and (d) the effects of TNFalpha, or antimycin A, were sensitive to catalase. The TNFalpha-dependent inhibition of complex III appears to be mediated by ceramide. Three lines of evidence support this inference: (a) a synthetic cell-permeable ceramide analogue reproduced all the effects of TNFalpha, (b) TNFalpha promoted the formation of ceramide via a mechanism sensitive to inhibition of sphingomyelinases by tricyclodecan-9-yl-xanthogenate and imipramine, and (c) the TNFalpha-mediated enhancement of the tert-butylhydroperoxide-induced DNA-damaging response was prevented under conditions in which ceramide formation was inhibited.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antimycin A, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Ceramides, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Single-Stranded, http://linkedlifedata.com/resource/pubmed/chemical/Electron Transport Complex III, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/N-acetylsphingosine, http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine, http://linkedlifedata.com/resource/pubmed/chemical/Superoxides, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/tert-Butylhydroperoxide
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
56-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
TNFalpha enhances the DNA single-strand breakage induced by the short-chain lipid hydroperoxide analogue tert-butylhydroperoxide via ceramide-dependent inhibition of complex III followed by enforced superoxide and hydrogen peroxide formation.
pubmed:affiliation
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino, Urbino, 61029, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't