Linked Life Data

17550273

Source:http://linkedlifedata.com/resource/pubmed/id/17550273

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-7-16
pubmed:abstractText
Cellular oxidative stress causes increased lipid peroxidation with the concomitant formation of DNA and protein reactive bifunctional electrophiles. Glutathione (GSH) detoxifies these bifunctional electrophiles by forming GSH adducts. Several years ago we discovered 4-oxo-2(E)-nonenal (ONE) as a major bifunctional electrophile derived from lipid hydroperoxides. We have now made the unexpected discovery that glutathione-S-transferase (GST)-mediated GSH addition to ONE occurs primarily to C-1 of the alpha,beta-unsaturated ketone rather than to C-3 of the alpha,beta-unsaturated aldehyde. The resulting intermediate rapidly undergoes two intramolecular cyclizations followed by two separate dehydration reactions to provide an unusual thiadiazabicyclo-ONE-GSH adduct (TOG). Quantification of intracellular TOG was performed using stable isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry after the addition of ONE to cells or as an endogenously derived adduct during peroxide-induced oxidative stress. TOG represents the first member of a new class of thiadiazabicyclo GSH adducts that are formed through GST-mediated addition of GSH to reactive intermediates containing the ONE motif during intracellular oxidative stress. ONE formation can potentially result from free radical pathways as well as cyclooxygenase- and lipoxygenase-mediated pathways. Its aldo-keto reductase-mediated reduction product, 4-oxo-2(E)-nonenol (ONO), was also formed and converted to GSH adducts similar to those formed by 4-hydroxy-2(E)-nonenal (HNE). ONO is isomeric with HNE; therefore, protein and peptide adducts ascribed to arise solely from reactions with endogenous HNE will need to be re-appraised.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1008-18
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
A novel 4-oxo-2(E)-nonenal-derived endogenous thiadiazabicyclo glutathione adduct formed during cellular oxidative stress.
pubmed:affiliation
Centers for Cancer Pharmacology and Excellence in Environmental Toxicology, University of Pennsylvania School of Medicine, 854 BRB II/III, 421 Curie Boulevard, Philadelphia Pennsylvania 19104-6160, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural