MRP4

..of 1 microM trequinsin, an inhibitor of cGMP-binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4/5, whereas 50 microM trequinsin partially inhibited cGMP transport...

..The function of MRP3 in other tissues, notably the gut and the adrenal cortex, remains to be defined. MRP4 and MRP5 have attracted attention by their ability to transport cyclic nucleotides and many nucleotide analogs...

..Recently, we identified the multidrug resistance protein (MRP) 4 as a luminal efflux transporter for urate in the proximal tubule...

..3. Both MRP4 and MRP5 are able to mediate the transport of cyclic nucleotides and confer resistance to certain antiviral and ..

..these scFv antibodies failed to react with tumor cells overexpressing other MRP proteins, including MRP1, MRP2, MRP4 and MRP5. M25 and M58 also bound to viable neurospheres. Iodogen-labeled scFvs demonstrated a yield of 56-76%...

..We observed frequent MRP4 overexpression in aggressive primary neuroblastoma, a disease for which we have previously shown MRP1 to be a ..

..Thus, as an efflux pump for the proinflammatory mediators LTB(4) and LTC(4), ABCC4 may represent a novel target for anti-inflammatory therapies...

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..Two recently described members of the multidrug resistance protein family, MRP4 and MRP5, might be involved in this process, because they transport the 3',5'-cyclic nucleotides, cAMP and cGMP, ..

The multidrug resistance protein MRP4, a member of the ATP-binding cassette superfamily, confers resistance to purine-based antiretroviral agents. However, the antiviral agent ganciclovir (GCV) has not been shown to be a substrate of MRP4...

..Recently, it has been shown that Mrp4 is induced in the livers of Fxr ((-/-)) mice, which have increased levels of serum bile acids...

..resveratrol, naringenin, daidzein and hesperetin with the multidrug-resistance-associated proteins, MRP1, MRP4 and MRP5...

..In inside-out membrane vesicles derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and ATP-dependent uptake of prostaglandin E1 (PGE1) and PGE2...

..ABC) transporter genes and the multidrug resistance associated proteins (MRP1/ABCC1, MRP2/ABCC2, MRP3/ABCC3, MRP4/ABCC4, MRP5/ABCC5, MRP6/ABCC6, MRP7/ABCC10, MRP8/ABCC11 and MRP9/ABCC12) belong to the ABCC family which contains ..

..At days 14 and 17, fetal membranes expressed higher mRNA levels of the efflux transporters Mrp2 (7-fold), Mrp4 (5-fold), Mrp5 (3-fold), Mrp6 (12-fold), Bcrp (2-fold), and Mate-1 (7-fold) than placenta...

..of uptake transporters Ntcp and Oatp4 was significantly increased, as were sinusoidal efflux transporters Mrp3 and Mrp4. Although in PB/LCA cotreated mice, the only significant change compared with LCA-only treatment was an increase in ..

..In contrast, multidrug resistance-associated proteins Mrp1, Mrp2, Mrp3, and Mrp4, as well as multidrug resistance proteins Mdr1a and Mdr1b genes, were increased following APAP...

..Both PGE(1) and PGE(2) are known high-affinity substrates of MRP4, but not MRP1, MRP2, MRP3 and MRP5. LTC(4) is a substrate of MRP1, MRP2, MRP3, and MRP6-8...

..1-fold higher resistance to cisplatin, and they expressed higher levels of MRP2 (6.29-fold), MRP3 (3.2-fold), MRP4 (11.3-fold) and MRP5 (3.39-fold) mRNAs than the wild-type cells by using real-time PCR...

..b>Mrp4 is the most significantly upregulated transporter in mouse liver following APAP treatment...

..We previously reported the isolation of three human MRP/cMOAT-related transporters, MOAT-B (MRP4), MOAT-C (MRP5) and MOAT-D (MRP3). In the present study we describe the fourth MRP/cMOAT-related transporter...

..liver, Mrp2 transports bilirubin-glucuronide, glutathione (GSH), and drug conjugates into bile, whereas Mrp3 and Mrp4 efflux these entities into blood...

..multidrug resistance-associated proteins (Mrps) was increased in livers of ob/ob mice, particularly with Mrp4 expression being elevated by at least 6-fold and Mrp2 expression at least 3-fold in livers of ob/ob mice...

..Renal protein expression of Mrp2 increased, whereas that of Mrp4 remained unchanged in both genders of Nx rats...

..blot analysis demonstrated increased levels of CYP3A1/2 and Mrp2 in SCRH pretreated with DEX; interestingly, Mrp4 expression was increased in SCRH after BSO exposure...

..Their structure, function, and substrate specificity have been studied intensively, but little is known about their clinical relevance in malignant diseases...

..To further define the MRP/cMOAT subfamily of transporters, we used EST probes to isolate complementary DNAs for two related transporter proteins, MOAT-C and MOAT-D...

..Expression of MRP1, MRP3, MRP4, and MRP5 in human pancreas and pancreatic carcinoma has been reported...

..cMOAT or MRP2, encoding the canalicular multispecific organic anion transporter; and four homologues, called MRP3, MRP4, MRP5, and MRP6. The most recently discovered member of the family, MRP6, is analyzed in this report...

..Cisplatin-induced renal injury increased mRNA and protein levels of the efflux transporters Mrp2, Mrp4, Mrp5, Mdr1a and Mdr1b. Uptake transporters Oatp2a1 and Oatp2b1 mRNA were also up-regulated following cisplatin...

..In this study the expression of the MRP2, MRP3, MRP4, MRP5, and SMRP genes was measured using TaqMan real-time polymerase chain reaction (PCR) in 103 children with ..

..Three other MRPs (MRP3, MRP4 and MRP5) were detected by RT-PCR in both cell lines, whereas MRP2 was not expressed...

..With respect to hepatocytes, activated HSCs expressed high levels of Mrp1 and comparable levels of Mrp3, Mrp4, Mdr1a, and Mdr1b but not the hepatocyte-specific transporters bile salt export pump, Mrp2, and Mrp6...

..3-fold) and decreased levels of Oct2 to 50% of control kidneys. Conversely, efflux transporters Mrp2, Mrp4, and Bcrp were increased 5.4-fold, 2-fold, and 1...

..work has shown that at least three members of the family of human Multidrug Resistance-associated Proteins (MRPs), MRP4, 5 and 8, are able to transport some nucleoside-monophosphate analogs...

The purpose of the present study was to investigate the role of multidrug resistance-associated protein 4 (MRP4) in the tubular secretion of cephalosporin antibiotics...

..Lat1, Mrp1 and Mrp4 were detected on the basal-lateral surface of lateral ventricle choroid plexus epithelial cells...

..1 +/- 0.6 mM). Human MRP4 (ABCC4), which has recently been localized to the apical membrane, expressed in Sf9 cells had a much higher ..

..b>Mrp4 induction in the liver and kidney correlated with bile acid levels and was observed in UDCA-fed and CA-fed FXR(-/-) ..

..OCT)1, 2, and 3; OCTN1; organic anion-transporting polypeptide (OATP)3; and multidrug resistance (MRP)1 and MRP4] in nasal respiratory mucosa, olfactory mucosa, and olfactory bulb to the level of expression of these transporters ..

..receptors, P2Y1ATP receptors and several members of the ATP binding cassette (ABC) transporters including MRP1, MRP4 and Pgp. The increase in [Ca2+]i elicited by LTD4 (0...

..4 × 10(-10), R = -0.376). The thiopurine cellular circulation and genetic polymorphisms for genes encoding the proteins involved should be incorporated into future studies of thiopurine drug therapy and effect...

..Mrp3 was moderately induced in ICAM(-/-), lpr, and endotoxin-resistant mice, whereas Mrp4 was only induced in the endotoxin-resistant strain...

..polypeptide (OATP)-B, OATP-C, and OATP8 and the efflux pumps multidrug resistance-associated protein (MRP) 2, MRP3, MRP4, and breast cancer resistance protein were also down-regulated at mRNA levels in human hepatocytes treated by IL-..

..We aimed to study the molecular mechanisms of action of these drugs in humans...

..such as Ntcp, Oct1, and Oatp2 were decreased and basolateral ATP-binding cassette transporters such as Mrp3 and Mrp4 were increased by the CCl(4) treatment...

..overexpressing the proximal tubular apical efflux transporters human multidrug resistance protein (MRP) 2/ABCC2 and MRP4/ABCC4. MTX was transported by MRP2 and MRP4 with Km values of 480 +/- 90 and 220 +/- 70 microM, respectively...

Multidrug resistance protein 4 (MRP4; ABCC4) is a member of the ATP-binding cassette superfamily of membrane transport proteins and confers resistance to nucleoside and nucleotide analogues as well as camptothecin derivatives...

..These components each affect androgen-regulated gene expression. The objective of this work was to determine the combined effects of selenium and isoflavones on androgen-regulated gene expression in rat prostate...

..5 pmol/min/mg prot, while MRP1 (ABCC1) and MRP4 (ABCC4) had little to no uptake...

..This murine model of familial PCT affords the opportunity to study changes in porphyrinogen and porphyrin accumulation and transport in the absence of exogenous factors that alter P450 activity and transmembrane transporters...

..there were striking increases in both mRNA and protein levels of multidrug resistance-associated protein (Mrp) 3, Mrp4, and breast cancer resistance protein, as well as increased Mrp2 protein...

..Expression of mRNA of other putative urate transporters (UAT, MRP2, MRP4, Oatv1) was unaffected in the knockouts, as were general indexes of renal function (glomerular filtration rate, ..

Multiple drug resistance protein 4 (MRP4, ABCC4) belongs to the C subfamily of the ATP-binding cassette (ABC) transporter superfamily and participates in the transport of diverse antiviral and chemotherapeutic agents such as 6-..

..A single PFDA dose (80 mg/kg) administered to mice increased hepatic Mrp3 (fourfold) and Mrp4 (31-fold) mRNA expression...

..These findings indicate that pharmacological activation of VDR enhances metabolism of bile acids, especially urinary excretion. The results confirm that VDR acts a regulator of bile acid metabolism in vivo...

..for the hepatic basolateral membrane export transporters, multidrug resistance-associated protein 3 (Mrp3) and Mrp4, and for the apical bilirubin transporter, Mrp2, were all increased...

..of uric acid by human URAT1 and others inhibit the transport of uric acid mediated by human URAT1, OAT1, OAT3 and MRP4 in vitro...

..Our data provide a basis for the assessment of the role of uptake transporters and efflux pumps in the accessibility of human gliomas for chemotherapeutic agents...

..Similarly, APAP treatment increased hepatic Mrp3 and Mrp4 mRNA and protein in WT, but not Nrf2-null mice...

..In this study, we used multidrug resistance protein 4 (MRP4)-expressing cell lines and MRP4 knock-out mice as model systems and wound healing assays as the experimental system ..

..Genotyping of AIDS patients for ABCB1 variation may help predict outcome and potentially could help guide treatment strategies...

..The aim of this study was to determine the association between polymorphisms in genes encoding drug transporters and KTD in Japanese patients treated with tenofovir...

..Alteration of MRP3, MRP4, hCNT1 and hCNT3 expression was observed in MUC4-KD cells, but only hCNT1 alteration was correlated to MUC4 ..

..This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of ..

..cisplatin only treated rats, the induced renal injury increased protein levels of the efflux transporters MRP2 and MRP4 while expression of OAT1, OAT3, OCT1 and OCT2 was reduced...

..Pregnancy decreased the expression of Mdr1b, Mrp4, and 5 proteins and increased the mRNA and protein expression of Mrp3 by 50-60%...

..new molecular targets explaining these results, we found a significant down-regulation of the hepatic GSH exporter MRP4 and an up-regulation of the HCys exporter Slco1a4...

..These results indicate that, besides their possible therapy-modulating effects, xenobiotic transporters may contribute significantly to other keratinocyte functions, such as cell proliferation...

..transporter genes (MRP1, -2, -3, -4, -5, -6, p-gp, and BCRP), the protein expression and localization of MRP1, MRP4, and MRP5, and the functionality of MRP1 efflux pumps at different maturation stages of undifferentiated human ..

..Recently we reported that the human ATP-binding cassette (ABC) transporter multidrug resistance protein 4 (MRP4 and ABCC4) is required for the migration of human DC...

..Although there are several PG transporters such as multidrug resistance-associated protein 4 (MRP4), organic cation transporter 1 (OCT1) [solute carrier (SLC) 22A1], organic anion transporter 1-3 (OAT1-3) [SLC22A6-..

..In contrast to previously reported heterozygous patients with renal hypouricemia type 2, we did not find even slight hypouricemia and found no decrease in the FE-UA of the heterozygous parents of the reported siblings...

..are implicated in xenobiotic exclusion from the brain, including ABCB1 (PGP), ABCG2 (BCRP), ABCC1 (MRP1), ABCC4 (MRP4), and ABCC5 (MRP5)...

..The multivariate approach presented in this study should aid in predicting signalling pathways that participate either directly or indirectly in regulating hepatic drug disposition...

..In addition, mRNA expression of multidrug resistance protein 4 (MRP4, ABCC4), supposed to take part in antiviral and anticancer drug transport from cells, was up-regulated after COX-1 ..

..Analysis at the mRNA (real-time PCR) and protein (Western blotting) levels revealed an overexpression of Mrp2 and Mrp4. Mrp4 transcripts, however, were overwhelmingly predominant (45% [wild-type cells] to 95% [ciprofloxacin-resistant ..

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..Expression of multidrug resistance Mdr1a/1b/MDR1/P-gp, Mrp1/MRP1, and Mrp4/MRP4 is confirmed by quantitative polymerase chain reaction and immunoblotting analysis in TM4 cells and HSECs...

..Oatp1a1 and Oatp1b2 mRNA levels were decreased in WT mice fed the MCD diet, whereas the efflux transporter Mrp4 was increased...

..b>MRP4 overexpression is associated with high-level resistance to the nucleoside analogues 9-(2-phosphonylmethoxyethyl) ..

..The objective of this study was to characterize efflux proteins (P-glycoprotein (P-gp), multidrug resistance proteins (MRP1-6) and breast cancer resistance protein (BCRP)) of retinal pigment epithelium (RPE) cell lines...

..The CYP2B6*6 allele, multidrug resistance-associated protein 4 (MRP4) 1497C → T, and gamma-glutamyltranspeptidase (GGT) were identified as major factors influencing the apparent EFV ..

..Our data indicate that transporter expression and activity patterns in the different trout cell lines are irrespective of the tissue of origin, but are determined by factors of cell cultivation...

..cells, they expel drugs back to the external medium (if located at the apical side [P-glycoprotein, BCRP, MRP2, MRP4 in the kidney]) or to the blood (if located at the basolateral side [MRP1, MRP3, MRP4, MRP5]), modulating thereby ..

..Keap1-kd mice have high-level expression of hepatic Mrp2, Mrp3, and Mrp4 relative to WT mice...

..Hybridization studies using specific probes indicated that this new mRNA form probably corresponded to the 3.4-kb mRNA, one of the two 15-PGDH mRNAs previously detected in Northern blot analysis...

..of the ATP-Binding cassette (ABC) family, P-glycoprotein (Pgp), multidrug-resistance associated protein 4 (MRP4) and breast cancer resistance protein (BCRP), located on endothelial cells lining brain vasculature play important ..

..Ost) α and multidrug resistance protein 1 and kidney multidrug resistance-associated protein (Mrp) 2, Mrp3, and Mrp4 were significantly greater in the sham Bcrp KO versus sham WT mice...

..In this study, the role(s) of organic anion transporter type 1 (OAT1) and multidrug-resistant protein type 4 (MRP4) in transport and regulation of tenofovir in proximal tubules were assessed...

..The results contribute to a better understanding of the cellular transport characteristics of nucleoside drugs...

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..001), respectively, in comparison with controls, whereas multidrug resistance-associated protein 4 (MRP4) mRNA was upregulated by 85% (P = 0.02). Bile salt export pump and MRP2 staining were downregulated in septic pigs...

..Gemifloxacin was also a weaker substrate than ciprofloxacin for the efflux transporter Mrp4 active in J774 macrophages...

..Findings suggest that there may be a vectorial shift from hepatic to renal excretion for some substrates in T1DM...

..Their functions may be related to glutathione and lipid homeostasis, secretion of lipid mediators, cell protection as well as drug transport...

..To evaluate the relationship of hypoxia-inducible factor (HIF)-1alpha expression with chemotherapy response in gastric cancer and its clinical outcome...

..To assess whether the poor prognosis of ZAP70-positive B-cell chronic lymphocytic leukemia (CLL) is associated with the overexpression of ABC transporter genes that are responsible for pleiotropic drug resistance...

..b>MRP4 and MRP5 resemble each other more closely than they resemble MRPs 1-3 and confer resistance to purine and ..

..3-fold) and protein (2.2-fold), respectively, in gp120 treated astrocytes while Mrp4 mRNA or protein expression was not changed...

..protein T16; Cytokine Receptor-like Factor, and three members of the Proliferin gene family, Proliferin- 1; Mrp4, and proliferin- related protein (PRP)...

..and others have determined that the first three of the newly identified family members to be examined, MRP3, MRP4 and MRP5, are also drug pumps involved in cellular resistance to anticancer agents...

..e., OAT1 and OAT3) and two distinct luminal transporters (i.e., MRP2 and MRP4)...

..e., OAT1 and OAT3) and two distinct luminal transporters (i.e., MRP2 and MRP4)...

..e., OAT1 and OAT3) and two distinct luminal transporters (i.e., MRP2 and MRP4)...

..and/or MRP2 (ABCC2)), nucleoside influx (OAT1, OAT3, and OAT4, CNT-1 and-2, and ENTs), and nucleoside efflux (MRP4 (ABCC4), MRP5 (ABCC5) are expressed and functional in lymphocytes...

The hypothesis of this proposal is that the functional activities of the cAMP transporter (MRP4) and CFTR Cl- channel are physically and functionally coupled within the gut epithelial cells...

The hypothesis of this proposal is that the functional activities of the cAMP transporter (MRP4) and CFTR Cl- channel are physically and functionally coupled within the gut epithelial cells...

..findings, the studies in Specific Aim 1 are designed to test the hypothesis that the ABC transporters Mrp3 and Mrp4 are responsible for the residual bile acid transport and serve to protect the ileal epithelium from bile acid-..

..the last funding period were directed to elucidating the function and molecular regulation of the ABC transporter, Mrp4. The current proposal represents an evolution of this work, based upon recent studies from this laboratory using ..

..the last funding period were directed to elucidating the function and molecular regulation of the ABC transporter, Mrp4. The current proposal represents an evolution of this work, based upon recent studies from this laboratory using ..

..not express the Mrp2 protein, and Madin-Darby canine kidney (MDCK) cells stably transfected with OAT1 and MRP2 or MRP4. We will first examine the effect of DMPS and DMSA on the handling and disposition of CH3Hg+ and Hg2+ in control ..

..and others have determined that the first three of the newly identified family members to be examined, MRP3, MRP4 and MRP5, are also drug pumps involved in cellular resistance to anticancer agents...

..and the CSF is largely controlled by drug efflux transporters, including P-pg, multi-drug resistance protein 4 (MRP4), and the breast cancer resistance protein (BCRP or ABCG2)...

..The APAP-detoxifying transporter MRP4 is also likely under the positive control of LXR...

..The APAP-detoxifying transporter MRP4 is also likely under the positive control of LXR...

..This was the case for the ABC transporter Mrp4 that was an orphan ABC transporter until our studies first determined that it was unique in its ability to ..

..will be sought as well as the effects of cholestasis on the expression of organic cation transporters (Octs) and Mrp4 in liver, kidney and intestine and the ameliorating effects of ursodeoxycholic acid...

..They will utilize transgenic mice deficient in Mrpl, Mrp4, or GGT...

..During the current funding cycle we determined that the efflux transporter Mrp4 is the most significantly induced MRP during APAP hepatotoxicity...

..They will utilize transgenic mice deficient in Mrpl, Mrp4, or GGT...

..make use of cloned proteins isolated in model cell systems, and are designed to test the hypothesis that MRP2 and MRP4, both of which are localized to the apical membrane of RPT cells, contribute to the secretion of OAs primarily ..