Linked Life Data

9667737

Source:http://linkedlifedata.com/resource/pubmed/id/9667737

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-7-30
pubmed:abstractText
Cancer chemoprevention is inhibition of neoplastic disease by naturally occurring or synthetic chemical agents. Dithiolethiones inhibit production of experimentally produced tumors by elevating the expression of several genes that encode for known cytoprotective enzymes. In an effort to discover additional molecular mechanisms mediating chemoprevention, cDNA clones representing a gene that is transcriptionally activated by dithiolethiones, hence named dithiolethione-inducible gene-1 (DIG-1), were isolated from rat liver via differential hybridization screening. The deduced amino acid sequence of DIG-1 was found to have 80% identity with the human liver enzyme leukotriene B4 (LTB4) 12-hydroxydehydrogenase. DIG-1, purified >400-fold from the liver of rats dosed with 1,2-dithiole-3-dithiolethione, possessed an NADP+-dependent activity to convert LTB4 to 12-oxo-LTB4. Kinetic analysis of DIG-1 revealed apparent Km and Vmax values of 28 mM and 8.1 nmol 12-oxo-LTB4 formed/min/mg purified protein respectively. Since LTB4 is a potent chemotactic factor and stimulator of production of reactive oxygen species from neutrophils, the effects of DIG-1 on these LTB4-mediated processes were examined. Pre-incubation of LTB4 with purified rat hepatic DIG-1 greatly diminished LTB4-stimulated migration of neutrophils. In addition, pre-incubation of LTB4 with purified rat hepatic DIG-1 reduced LTB4-stimulated production of superoxide anions in neutrophils, as evidenced by decreased lucigenin-derived chemiluminescence. These results suggest that DIG-1-catalyzed dehydrogenation of LTB4 to 12-oxo-LTB4 inhibits the pro-inflammatory actions of LTB4. Consequently, elevation of LTB4 catabolism via enhanced DIG-1 activity may suppress inflammatory processes implicated in tumorigenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
999-1005
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Identification of dithiolethione-inducible gene-1 as a leukotriene B4 12-hydroxydehydrogenase: implications for chemoprevention.
pubmed:affiliation
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't