Disease relevance of Abcc3

• Reduction of endogenous VDR expression in colon adenocarcinoma MCA-38 cells by siRNA transfection was associated with reduced constitutive and inducible expression of the Mrp3 gene [1].

High impact information on Abcc3

• This results in increased levels of M3G in liver and bile, a 50-fold reduction in the plasma levels of M3G, and in a major shift in the main disposition route for morphine and M3G, predominantly via the urine in WT mice but via the feces in Mrp3(-/-) mice [2].
• Western analyses revealed that Mrp4, but not Mrp3, was significantly increased after CBDL in wild-type mice [3].
• Because Mrp3 preferentially transports glucuronide conjugates, we investigated the in vivo disposition of acetaminophen (APAP) and its metabolites [4].
• Mrp3+/+ and Mrp3-/- knockout mice received APAP (150 mg/kg), and bile was collected [4].
• MRP3 is an ABC transporter localized in the basolateral membrane of epithelial cells such as hepatocytes and enterocytes [4].

Biological context of Abcc3

• We hypothesized that induction of Mrp3 would be associated with Lrh-1 up-regulation and would require intact cytokine signaling [5].
• We have characterized the substrate specificity and mechanism of transport of the human multidrug resistance-associated protein 3 (MRP3) [6].

Anatomical context of Abcc3

• The function of MRP3 in other tissues, notably the gut and the adrenal cortex, remains to be defined [7].

Associations of Abcc3 with chemical compounds

• The basolateral excretory clearance of acetaminophen glucuronide, 4-methylumbelliferyl glucuronide, and harmol glucuronide was reduced by approximately 96, approximately 85, and approximately 40%, respectively, in the livers of Abcc3(-/-) mice [8].
• In the livers of Abcc3(-/-) and Abcc4(-/-) mice, the basolateral excretory clearance of acetaminophen sulfate was reduced approximately 20 and approximately 20%, 4-methylumbelliferyl sulfate was reduced approximately 50 and approximately 65%, and harmol sulfate was decreased approximately 30 and approximately 45%, respectively [8].
• Treatment of mice with VD3 or LCA demonstrated in vivo modulation of the Mrp3 gene in colon but not in the liver [1].
• Functional analysis of a murine Mrp3 promoter reporter construct revealed vitamin D receptor (VDR)-dependent activation by 1,25-dihydroxyvitamin D(3) (VD3), 9-cis-retinoic acid (RA), and the cholestatic secondary bile acid, lithocholic acid (LCA) [1].
• In liver, PCN induced the expression of Oatp1a4 and Mrp3 mRNA in wild-type (WT) mouse liver, but not in PXR-null mice [9].

Other interactions of Abcc3

• These results provide the first direct evidence that Mrp3 and Mrp4 participate in the hepatic basolateral excretion of sulfate conjugates, although additional mechanism(s) are likely involved [8].
• Hepatic Abcc3 protein levels, determined by immunoblot analysis, were approximately 60% higher in Abcc2-/- mice than in wild-type mice [10].
• The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry [11].
• The MRP/plf-mRNA species expressed in the skin were predominantly plf1 and mrp3 as determined by gene-specific restriction enzyme sites within the RT-PCR products [12].

References