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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-7-7
pubmed:abstractText
The multidrug resistance protein MRP1 and its isoform MRP2 are involved in ATP-dependent glutathione S-conjugate transport and have similar substrate specificities. MRP2 mediates hepatic organic anion transport into bile. The physiological function of MRP1 in hepatocytes is unknown. Previous results show that MRP1 expression is low in quiescent hepatocytes but increased after SV40 large T antigen immortalization, suggesting a relationship with cell proliferation. Therefore, we determined mrp1 and mrp2 expression in rat hepatocytes in relation to the cell cycle. By varying cell density we obtained cultures that are mainly in G1 (high density) or have progressed into the S-phase or beyond (low density). In both cultures mrp1 mRNA and protein levels are increased, concomitantly with the disappearance of mrp2. This switch from mrp2 to mrp1 occurs in the G1 phase of the cell cycle and is associated with a decreased cell polarity. Mrp1 is located on lateral membranes or on intracellular vesicles, depending on whether cell-cell contact is established. In both locations mrp1 contributes to cellular glutathione S-conjugate efflux and protects against oxidative stress-inducing quinones. We conclude that a switch in expression from the apically located mrp2 to the basolaterally located mrp1 preserves glutathione S-conjugate transport in hepatocytes entering the cell cycle and protects against certain cytotoxic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
112 ( Pt 9)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1395-404
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10194418-ATP-Binding Cassette Transporters, pubmed-meshheading:10194418-Animals, pubmed-meshheading:10194418-Carrier Proteins, pubmed-meshheading:10194418-Cell Count, pubmed-meshheading:10194418-Cell Cycle, pubmed-meshheading:10194418-Cell Membrane, pubmed-meshheading:10194418-Down-Regulation, pubmed-meshheading:10194418-Drug Resistance, Multiple, pubmed-meshheading:10194418-G1 Phase, pubmed-meshheading:10194418-Liver, pubmed-meshheading:10194418-Male, pubmed-meshheading:10194418-Membrane Transport Proteins, pubmed-meshheading:10194418-Multidrug Resistance-Associated Proteins, pubmed-meshheading:10194418-Oxidative Stress, pubmed-meshheading:10194418-Rats, pubmed-meshheading:10194418-Rats, Wistar, pubmed-meshheading:10194418-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10194418-S Phase
pubmed:year
1999
pubmed:articleTitle
Glutathione S-conjugate transport in hepatocytes entering the cell cycle is preserved by a switch in expression from the apical MRP2 to the basolateral MRP1 transporting protein.
pubmed:affiliation
Dept of Internal Medicine, Div. of Gastroenterology and Hepatology, University Hospital Groningen, PO Box 30001, The Netherlands. j.roelofsen@med.rug.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't