Linked Life Data

12623073

Source:http://linkedlifedata.com/resource/pubmed/id/12623073

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-3-7
pubmed:abstractText
4-hydroxynonenal (4HNE) is a major product of peroxidative membrane lipid destruction and exerts a variety of deleterious actions through formation of covalent adducts with cellular nucleophiles. Consequently, a number of cellular enzyme systems exist that are capable of detoxifying this reactive aldehyde by oxidation, reduction, or conjugation with glutathione. In this investigation we characterize the multidrug resistance-associated protein 2 (MRP2) as the primary transmembrane transport protein in hepatocytes responsible for extracellular export of 4HNE-glutathione conjugate (HNE-SG) from the intracellular site of its formation. Suspensions of freshly isolated hepatocytes (10(6) cells/ml) prepared from either wild-type (WT) Wistar rats or TR(-) rats possessing a mutated Mrp2 gene were incubated with 4HNE (50 nmol/10(6) cells). The formation of 4HNE metabolites, 4-hydroxynonenoic acid (HNA) and HNE-SG, was quantified in the intracellular and extracellular fractions. These studies demonstrated that freshly isolated hepatocytes from both WT and TR(-) rats formed and exported the oxidized metabolite (HNA) to similar extents. Likewise, both populations of hepatocytes displayed nearly identical rates of glutathione conjugation with 4HNE. However, the rate of HNE-SG export from TR(-) hepatocytes was approximately fourfold less than that of WT hepatocytes. In TR(-) hepatocytes, HNE-SG accumulated and remained predominantly intracellular throughout the time course, suggesting an absence of compensatory export by other hepatocellular transporters. In conclusion, these data demonstrate that although WT and TR(-) hepatocytes are similar in their conjugative and oxidative metabolism of 4HNE, export of 4HNE-SG is mediated by the MRP2 transporter, a transport system distinct from that involved in HNA efflux.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
411
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
243-50
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Characterization of multidrug resistance-associated protein 2 in the hepatocellular disposition of 4-hydroxynonenal.
pubmed:affiliation
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.