Upregulation in the expression of multidrug resistance protein Mrp1 mRNA and protein by increased bilirubin production in rat

Earlier studies suggest that Mrp1 may mediate ATP-dependent cellular extrusion of unconjugated bilirubin (UCB). We studied the serial responses of expression of Mrp1 mRNA and protein in rats with increased bilirubin production due to hemolysis induced by phenylhydrazine (PHZ) treatment. Mrp1 mRNA wa...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-11, Vol.311 (4), p.891-896
Main Authors: Cekic, Dean, Bellarosa, Cristina, Garcia-Mediavilla, Maria Victoria, Rigato, Igino, Pascolo, Lorella, Ostrow, J.Donald, Tiribelli, Claudio
Format: Article
Language:English
Subjects:
Animals
ATP Binding Cassette Transporter, Subfamily B, Member 1 - blood
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism
Bilirubin - blood
Bilirubin - metabolism
Dose-Response Relationship, Drug
Heme-oxygenase
Hemolysis
Hemolysis - drug effects
Hemolysis - physiology
Liver - drug effects
Liver - metabolism
Male
Metalloporphyrins - pharmacology
Mrp1
Mrp1 gene
Organ Specificity
phenylhydrazine
Phenylhydrazines - pharmacology
Protoporphyrins - pharmacology
Rats
Rats, Wistar
RNA, Messenger - genetics
RNA, Messenger - metabolism
Spleen - drug effects
Spleen - metabolism
Transport
Unconjugated bilirubin
Up-Regulation - drug effects
Up-Regulation - physiology
Upregulation
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Summary:Earlier studies suggest that Mrp1 may mediate ATP-dependent cellular extrusion of unconjugated bilirubin (UCB). We studied the serial responses of expression of Mrp1 mRNA and protein in rats with increased bilirubin production due to hemolysis induced by phenylhydrazine (PHZ) treatment. Mrp1 mRNA was analyzed by quantitative PCR and protein by Western blot. Hepatic expression of Mrp1 mRNA and protein peaked at day 3 of PHZ treatment. Splenic expression of Mrp1 mRNA peaked within 24 h and returned to baseline at day 5 whereas Mrp1 protein expression peaked at day 3. Pretreatment with heme-oxygenase inhibitor, tin mesoporphyrin, blunted the increase in serum UCB and erased the overexpression of Mrp1 both in liver and spleen. Thus, the upregulation of Mrp1 in hemolysis is mediated by UCB and/or other products of heme oxygenase, further supporting a role of Mrp1 in UCB transport and protection from its cellular toxicity.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2003.10.081