Co-regulation of expression of phase II metabolizing enzymes and multidrug resistance-associated protein 2

Catania, Viviana A.; Pozzi, Enrique J. Sánchez; Luquita, Marcelo G.; Ruiz, María Laura; Villanueva, Silvina Stella Maris; Jones, Brett R.; Mottino, Aldo D.

doi:10.1016/s1665-2681(19)32119-2

Cited by 37 publications

(17 citation statements)

References 70 publications

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“…Glucuronidation activities in human tissues have exhibited a high degree of interindividual variation in human liver samples which can be partially explained by UGT1A4 [16,17,32,33]. Single nucleotide polymorphisms (SNPs) may influence the genetic role in variability.…”

Section: Discussionmentioning

confidence: 99%

Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples

Edavana

Penney²,

Yao-Borengasser

et al. 2015

Int J Cancer Res Mol Mech

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Anastrozole is an aromatase inhibitor (AI) used as adjuvant therapy for breast cancer. Anastrozole is subject to direct glucuronidation catalyzed by UDP-glucuronosyltransferase1A4 (UGT1A4). Interindividual variability in anastrozole glucuronidation may be affected by UGT1A4 SNPs. Interplay between drug metabolizing genes such as UGT1A4 and transporter genes may also be affected by genetic variability. Thus, we hypothesize that genetic variability in MRPs could influence anastrozole glucuronidation. The correlation between UGT1A4 and MRP2 or MRP3 transporter gene expressions and the correlation between MRP2 or MRP3 mRNA and anastrozole glucuronidation were analyzed in normal human liver samples. MRP2 and MRP3 mRNA levels were significantly correlated with UGT1A4 mRNA, with anastrozole glucuronidation and with each other (p<0.05). The data also demonstrated that MRP2 SNPs are positively correlated with MRP2 mRNA expression, while there was no association between MRP3 SNPs from this study and MRP3 expression. Significant correlations (p<0.05) between certain MRP2 SNPs (3972C>T, 2366C>T and −24C>T) and anastrozole glucuronidation were observed. There were no observed correlations between MRP3 SNPs and anastrozole glucuronidation. MRP2 polymorphisms have been identified as playing a role in the disposition of other drugs, and the data presented here indicate for the first time that MRP2 SNPs could influence anastrozole metabolism and contribute to interindividual variation in treatment responses.

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Section: Discussionmentioning

confidence: 99%

Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples

Edavana

Penney²,

Yao-Borengasser

et al. 2015

Int J Cancer Res Mol Mech

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“…As can be seen from Table 5, xenobiotics are also ligands of the above mentioned receptors; therefore, drugs entering the liver and kidney may bind to receptors, change their activi ties, and, consequently, change the expression of phase I and II enzymes and phase III transporters [36]. There are data on simultaneous coordinated stimulation of the hepatic expression of phase II enzymes and MRP2 and MRP3 transporters as a result of the activation of com mon nuclear receptors (PXR, FXR, and CAR) by ligands [61,62].…”

Section: Nuclear Receptors Involved In the Regulation Of Mrp Expressionmentioning

confidence: 99%

Gender-related differences in drug effects: The role of multidrug resistance proteins

Смирнова

2012

Hum Physiol

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Mechanisms of the involvement of multidrug resistance proteins (MRPs) in the formation of gen der related differences in drug effectiveness and adverse effects have been analyzed. The structure, tissue and cellular localization, substrate specificity, and functions of MRPs are discussed. The regulation of MRP expression and activity by endogenous metabolites, signaling compounds, including sex hormones, and phar maceutical agents is described. Nuclear receptors have been shown to play a role in the regulation of MRP expression. Data on gender related differences in the expression of MRPs and nuclear receptors that are involved in the induction of MRPs in the liver and kidney are presented. It is concluded that gender related differences in the expression and functional activity of MRPs in excretory organs (the liver and kidney) may significantly contribute to gender dependence of drug pharmacokinetics and effectiveness.

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“…Many of the metabolizing enzymes and efflux transporters share the same nuclear receptors, leading to the coordinated regulation of certain metabolizing enzymes and transport proteins (Annaert, 2007). Nuclear receptors that have been discovered include aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor α (PPARα), liver X receptor (LXR), farnesoid X receptor (FXR), and others (Catania et al, 2004). Caution is needed in interpreting the results of experiments involving nuclear receptors because the results are highly dependent on the ligand and the test system used.…”

Section: Coordinate Regulation Of Drug-metabolizing Enzymes and Efflumentioning

confidence: 99%

ABC Transporters in Intestinal and Liver Efflux

Morris

Gandhi

2011

Oral Bioavailability

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Co-regulation of expression of phase II metabolizing enzymes and multidrug resistance-associated protein 2

Cited by 37 publications

References 70 publications

Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples

Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples

Gender-related differences in drug effects: The role of multidrug resistance proteins

ABC Transporters in Intestinal and Liver Efflux

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