A Novel Decrease of Mrp3 Protein in Liver of β-Thalassemic Mouse
Mohammed Qaisiya *
Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Bldg Q AREA Science Park -Basovizza Campus 34149 Trieste, Italy.
Lucia de Franceschi
Department of Medicine, Section of Internal Medicine, University of Verona-AOUI-Verona, Verona, Italy.
Achille Iolascon
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, CEINGE- Advanced Biotechnologies, 80145 Naples, Italy.
Claudio Tiribelli
Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Bldg Q AREA Science Park -Basovizza Campus 34149 Trieste, Italy and Department of Medical Sciences, University of Trieste, 34149 Trieste, Italy.
Cristina Bellarosa
Fondazione Italiana Fegato ONLUS, Italian Liver Foundation ONLUS, Bldg Q AREA Science Park -Basovizza Campus 34149 Trieste, Italy.
*Author to whom correspondence should be addressed.
Abstract
Background: Hepatocytes have a fundamental system of efflux proteins that protect cells from toxic insults. Unconjugated bilirubin at higher concentration is toxic to cells and its intracellular accumulation is limited by the induction of efflux proteins such as Mrp3. In vivo studies showed an induction of hepatic Mrp3 expression in response to non-hemolytic hyperbilirubinemia as a compensatory mechanism to reduce UCB toxicity.
Study Design: In the present study, we analyzed the hepatic Mrp3 expression profile during hemolytic hyperbilirubinemia. We used β-thalassemic mouse and WT rodents treated with phenylhydrazine as an animal model of chronic and acute hemolysis, respectively.
Results: Unexpectedly, Mrp3 protein was 75% down-regulated in β-thalassemic mouse although Mrp3 mRNA was normal. Mrp3 mRNA was significantly induced in PHZ treated animals while again; Mrp3 protein was 60% down-regulated.
Conclusion: For the first time we observed a clear down-regulation for hepatic Mrp3 protein that linked to hemolysis, not to bilirubin. We hypothesize that a similar decrease for hepatic Mrp3 proteins is occur in hemolytic patients such as β-thalassemia.
Keywords: Hyperbilirubinemia, Mrp3, β-thalassemia, phenylhydrazine