Disease relevance of Abcc1

• These results indicate that the ATP-dependent release of leukotriene C4 by murine mastocytoma cells is mediated by murine Mrp [1].
• Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation [2].
• The aim of this work was to investigate the expression and activity of MRP and Pgp in the thymoma cell line, EL4 [3].
• Interestingly, endogenous Mrp/Plfs were detected using immunostaining both in mouse brain sections and the neuroblastoma cell line, Neuro-2a cells [4].
• Expression and regulation of breast cancer resistance protein and multidrug resistance associated protein 2 in BALB/c mice [5].

High impact information on Abcc1

• A decamer sequence, 5'-CGA-CCCCUCC-3', complementary to a conserved sequence adjacent to the enzymatic cleavage site on the mitochondrial RNA substrate, is present in the RNAase MRP RNA [6].
• Yeast site-specific ribonucleoprotein endoribonuclease MRP contains an RNA component homologous to mammalian RNase MRP RNA and essential for cell viability [7].
• We previously showed that Mrp1 protects against cytotoxic drugs at the testis-blood barrier, the oral epithelium, and the kidney urinary collecting duct tubules [8].
• Our results indicate that Mrp1 helps to limit tissue distribution of certain drugs and contributes to the blood-CSF drug-permeability barrier [8].
• Immunohistochemical staining revealed the presence of Mrp1 in the oviduct, uterus, salivary gland, and choroid plexus (CP) epithelium [8].

Chemical compound and disease context of Abcc1

• Intraabdominal sepsis down-regulates transcription of sodium taurocholate cotransporter and multidrug resistance-associated protein in rats [9].
• We demonstrated that high expression of MRP1 in murine hematopoietic cells reduces doxorubicin-induced leukopenia and mortality [10].
• Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1) [11].
• Proteus mirabilis, a common cause of urinary tract infection (UTI), expresses several types of fimbria including mannose-resistant/Proteus-like fimbriae (MRP), uroepithelial cell adhesin (UCA), renamed non-agglutinating fimbriae (NAF) by some authors, and P. mirabilis fimbriae (PMF), which are potentially involved in adhesion to the uroepithelium [12].

Biological context of Abcc1

• Glutathione (GSH), glutathione S-transferases (GSTs), and the multidrug resistance-associated protein 1 (MRP1) have been independently studied for their contributions to drug resistance [13].
• Increased expression through single cDNA transfection of GSTpi, gamma-glutamylcysteine synthetase (gamma-GCS) (regulatory plus catalytic subunits), or MRP1 enhanced resistance to a number of anticancer drugs [13].
• The deduced amino acid sequences of these fragments were identical with murine Mrp and 86.7% and 89.7% identical with the corresponding sequences of human MRP [1].
• To identify the Mrp repertoire of mouse brain and of astrocytes in particular, the expression of six mouse Mrps was investigated by reverse-transcription polymerase-chain reaction (RT-PCR) [14].
• Mrp4 is a member of the multidrug resistance-associated gene family that is expressed on the basolateral membrane of hepatocytes and undergoes adaptive upregulation in response to cholestatic injury or bile acid feeding [15].

Anatomical context of Abcc1

• Expression of P-glycoprotein (ABCB1) and Mrp1 (ABCC1) in adult rat brain: focus on astrocytes [16].
• We showed that P-gp was preferentially expressed in the endothelial component and Mrp1 in the astroglial component of the blood-brain barrier [16].
• Studies with isolated membrane vesicles from MBEC4 cells suggested the presence of a primary active transporter(s) for organic anions, and Western blot analysis indicated the presence of multidrug resistance associated protein (MRP1) and/or its related transporters on MBEC4 cells and freshly isolated rat cerebral endothelial cells [17].
• Together with the direction of transcellular transport, the basolateral localization of MRP on the choroid plexus was suggested [17].
• Mrp1 mRNAs have been detected by RT-PCR in rat brain isolated capillaries [16].

Associations of Abcc1 with chemical compounds

• Evaluation of the role of multidrug resistance-associated protein (mrp) 3 and mrp4 in hepatic basolateral excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in abcc3-/- and abcc4-/- mice [18].
• Coexpression of GSTpi with MRP1 conferred significant resistance above that seen for MRP1 alone to chlorambucil, etoposide, ethacrynic acid, and vincristine [13].
• Do multidrug resistance-associated protein-1 and -2 play any role in the elimination of estradiol-17 beta-glucuronide and 2,4-dinitrophenyl-S-glutathione across the blood-cerebrospinal fluid barrier [19]?
• Lines lacking both P-gp and Mrp1 were (compared with wild-type lines) hypersensitive to an even broader array of drugs, including epipodophyllotoxins (4-7-fold), anthracyclines (6-7-fold), camptothecins (3-fold), arsenite (4-fold) and Vinca alkaloids, especially vincristine (28-fold) [20].
• Leukotriene C4 secretion from normal murine mast cells by a probenecid-sensitive and multidrug resistance-associated protein-independent mechanism [21].

Regulatory relationships of Abcc1

• Moreover, Mrp1 was rather expressed than P-gp in parenchyma astrocytes and in glia limitans lining the meninges [16].
• 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 [22].

Other interactions of Abcc1

• However, the mechanisms by which the Oatp and Mrp genes are down-regulated are largely unknown [23].
• Indeed, choroidal and ependymal cells expressed Mrp1 rather than P-gp [16].
• No significant difference was observed in the expression of MDR1a, Mdr1b and Mrp-1 genes between wMNB and rMNB-MDL cells, however, a slight decrease was noticed in Mdr1 expression in some samples [24].
• TR-BBB cells express the mRNA of multidrug resistance associated protein 1 (MRP1) and a large neutral amino acid transporter, which consists of LAT1 and 4F2hc [25].
• The expression levels of Mrp/Plf mRNAs in mouse brains were low during the neonatal period, but higher in embryonic and adult stages, indicating Mrp/Plfs expression profiles are different in mouse brain and placenta [4].

Analytical, diagnostic and therapeutic context of Abcc1

• The analysis of Mdr and Mrp-1 expression was performed by RT-PCR using PCR specific primers to respective genes [24].
• In the present study, MRP expression in MC-9 cells was examined at the protein level by anti-MRP Ab, using flow cytometry and at the level of mRNA by PCR and Northern blot analyses [21].
• Northern blot analysis shows that the multidrug resistance-associated Mr 170,000-180,000 glycoprotein is overexpressed in the DC-3F/9-OH-E cells and that the overexpression is lost in the absence of selection [26].
• We have previously shown that abrogation of MRP expression by gene targeting leads to hypersensitivity to several drugs [27].
• Because intestinal and kidney epithelial cells are polarized cells endowed distinct secreting and absorptive ion and protein transport capacities, we investigated the tissue and cell distribution of MRP in adult mouse small intestine, colon, and kidney by immunohistochemistry [28].

References