Relevant bibliographies by topics / MRP4 (Multidrug Resistance Associated Protein 4)

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Academic literature on the topic 'MRP4 (Multidrug Resistance Associated Protein 4)'

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Published: 8 June 2023

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Journal articles on the topic "MRP4 (Multidrug Resistance Associated Protein 4)"

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Steinbach, Daniel, Susann Wittig, Gunnar Cario, Susanne Viehmann, Angelika Mueller, Bernd Gruhn, Ralf Haefer, Felix Zintl, and Axel Sauerbrey. "The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype." Blood 102, no. 13 (December 15, 2003): 4493–98. http://dx.doi.org/10.1182/blood-2002-11-3461.

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Abstract The family of multidrug resistance-associated proteins (MRPs) belongs to the superfamily of adenosine triphosphate-binding-cassette (ABC) transporters, which have the ability to function as outward pumps for chemotherapeutic drugs and therefore might be involved in drug resistance. 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 previously untreated acute lymphoblastic leukemia (ALL) (precursor B-cell ALL [B-ALL], n = 71; T-cell ALL [T-ALL], n = 32). All 5 genes were expressed with a great variability. Only MRP3 expression was associated with a significantly worse prognosis (P = .008). The median expression of MRP3 was 10-fold higher in T-ALL than in precursor B-ALL (P < .001) and 4-fold higher in male patients than in female patients (P < .001). The prognostic impact of MRP3 was independent of immunophenotype or sex. Higher levels of MRP3 were found in patients with a poor in vivo response to prednisone, but this could not be confirmed in an independent case-control study (40 patients) for prednisone response. In healthy donors, the median expression of MRP4 was 4-fold higher in bone marrow and 8-fold higher in CD34+ stem cells compared with peripheral blood (P = .002). Our results suggest that MRP3 is involved in drug resistance in childhood ALL. It therefore represents an interesting target to overcome multidrug resistance. High levels of MRP3 could possibly be the reason for the poorer prognosis of male patients or patients who have T-ALL. Similar to other members of the family of ABC transporters, MRP4 seems to be a marker for immature stem cells. (Blood. 2003;102:4493-4498)
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Ansari, Marc, Geraldine Sauty, Albert Moghrabi, and Maja Krajinovic. "Polymorphisms in Multidrug Resistance-Associated Protein Genes Are Associated with Worse Outcome in Childhood Acute Lymphoblastic Leukemia." Blood 110, no. 11 (November 16, 2007): 1443. http://dx.doi.org/10.1182/blood.v110.11.1443.1443.

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Abstract Methotrexate (MTX) is a key compound of chemotherapeutic regimens used in the treatment of childhood acute lymphoblastic leukemia (ALL). Inter-individual differences in response to this drug may cause treatment failures and adverse drug reactions. In particular, transporters of the adenosine triphosphate-binding cassette (ABC) family such as the ABCC (multidrug resistance-related protein, MRP) are involved in the efflux of this drug. The elimination of MTX may arise, among other factors, to be a major determinant of chemoresistance in leukemic blast cells. It has been demonstrated that ALL patients with high MRP expression had an unfavourable prognosis with relapsed patients showing a higher expression of MRP genes. The polymorphisms in MRP genes, particularly those in promoter region may explain differences in expression and thereby the inter-individual differences in clinical outcome for ALL children. We analyzed polymorphisms in five MRP genes (MRP1-MRP5). Two polymorphisms in MRP1, 7 in MRP2, 4 in MRP3, 8 in MRP4 and 3 in MRP5 gene, located in regulatory and coding gene regions were selected from NCBI dbSNP database. The polymorphisms were analyzed in 50 healthy individuals to estimate allele frequency, linkage disequilibrium, and haplotype phase. Variants sufficient to infer most common haplotypes were further analyzed in 243 children with de novo ALL, treated at Ste-Justine Hospital with multi-agent chemotherapy according to the Dana-Farber Cancer Institute protocols 87-01, 91-01, 95-01 and 2000-01. These polymorphisms/haplotypes were investigated for association with disease outcome. The polymorphisms of two genes, MRP1 and MRP3, appeared associated with event free survival (EFS). Individuals with the AA -genotype of A -1665G promoter polymorphism in MRP1 gene had worse EFS (69% vs. 85%, p=0.007) compared to patients with the GG or AG genotypes (Hazard ratio, HR=2.2 (IC 95%: 1.2–3.9). Carriers of A allele of G-1696A and A-189T polymorphisms in the MRP3 gene had a worse EFS (68% vs. 81%, p=0.016) compared to those with the GG or TT genotype respectively (HR=2,1 IC 95%: 1.1–3.8). The A alleles of both polymorphisms belong to the same haplotype. A-189 is uniquely tagging this haplotype, therefore the association between this haplotype and ALL outcome was also found. A-1696 is shared among this and additional haplotype, the latter not associated with EFS, rendering A-1696 allele less relevant for the prediction of ALL outcome. All associations remained significant in multivariate analysis after inclusion of the known prognostic factors. Similar results were obtained if disease free and overall survival were analyzed instead of EFS. As MRPs are also expressed in the blood-brain barrier, a possible correlation between these polymorphisms and type of relapse (isolated bone marrow or central nervous system) was analysed. No significant difference between the type of relapse and MRP1 or MRP3 described polymorphisms was seen. The variants MRP1 A-1665, and MRP3 A-189 localised in the regulatory region of these genes, have an impact on the outcome in ALL children and could predict differences in MTX response. Further analysis between these polymorphisms and MTX levels as well as combined effect with other at risk genotypes of the folate cycle should be analysed to determine the effect of MRP variants on the outcome of children with ALL.
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Donepudi, Ajay C., Gregory J. Smith, Oladimeji Aladelokun, Yoojin Lee, Steven J. Toro, Marisa Pfohl, Angela L. Slitt, et al. "Lack of Multidrug Resistance-associated Protein 4 Prolongs Partial Hepatectomy-induced Hepatic Steatosis." Toxicological Sciences 175, no. 2 (April 24, 2020): 301–11. http://dx.doi.org/10.1093/toxsci/kfaa032.

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Abstract Multidrug resistance-associated protein 4 (Mrp4) is an efflux transporter involved in the active transport of several endogenous and exogenous chemicals. Previously, we have shown that hepatic Mrp4 expression increases following acetaminophen overdose. In mice, these increases in Mrp4 expression are observed specifically in hepatocytes undergoing active proliferation. From this, we hypothesized that Mrp4 plays a key role in hepatocyte proliferation and that lack of Mrp4 impedes liver regeneration following liver injury and/or tissue loss. To evaluate the role of Mrp4 in these processes, we employed two-third partial hepatectomy (PH) as an experimental liver regeneration model. In this study, we performed PH-surgery on male wildtype (C57BL/6J) and Mrp4 knockout mice. Plasma and liver tissues were collected at 24, 48, and 72 h postsurgery and evaluated for liver injury and liver regeneration endpoints, and for PH-induced hepatic lipid accumulation. Our results show that lack of Mrp4 did not alter hepatocyte proliferation and liver injury following PH as evaluated by Ki-67 antigen staining and plasma alanine aminotransferase levels. To our surprise, Mrp4 knockout mice exhibited increased hepatic lipid content, in particular, di- and triglyceride levels. Gene expression analysis showed that lack of Mrp4 upregulated hepatic lipin1 and diacylglycerol O-acyltransferase 1 and 2 gene expression, which are involved in the synthesis of di- and triglycerides. Our observations indicate that lack of Mrp4 prolonged PH-induced hepatic steatosis in mice and suggest that Mrp4 may be a novel genetic factor in the development of hepatic steatosis.
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Horvah, L. G., L. Ho, J. G. Kench, J. A. Allen, G. L. Scheffer, P. D. Stricker, J. J. Grygiel, R. L. Sutherland, and S. M. Henshall. "Elevated multidrug resistance-associated protein 4 (MRP4) expression in localized prostate cancer—A potential androgen regulated protein." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 20022. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.20022.

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20022 Background: MRP4 is an ATP-binding cassette transporter and amphipathic anion efflux pump which transports prostaglandins, nucleoside analogues, glutamate and phosphate analogues. High MRP4 expression is prognostic of poor outcome in neuroblastoma and also correlates with MYCN amplification, suggesting regulation by this oncogene. Although MRP4 is known to be expressed in normal prostate epithelium, its expression in prostate cancer (PC) is undefined. This study aimed to define the pattern of expression of MRP4 in normal and malignant prostate tissue and assess the association with androgen exposure. Methods: 84 radical prostatectomy specimens from patients with clinically localized PC (22 neoadjuvant androgen ablation therapy, 62 no neoadjuvant treatment), 42 specimens of hyperplasia adjacent to PC and 16 cases of advanced PC were assessed for MRP4 expression using in situ hybridisation and immunohistochemistry. PC cell lines were assessed by immunoblotting. Results: There were significantly higher levels of MRP4 mRNA and protein expression in localized PC compared to hyperplasia (p=0.006). Conversely, MRP4 protein levels were significantly decreased in PCs treated with neoadjuvant androgen ablation therapy compared to cancers exposed to normal testosterone levels (p < 0.0001). There was also a trend towards decreased MRP4 expression in advanced PCs. Furthermore, immunoblotting revealed that MRP4 protein was more highly expressed in androgen-dependent (LNCaP) compared to androgen-independent (PC3/DU145) cell lines. In addition, in a panel of 14 normal human tissues only kidney and prostate tissue expressed MRP4 protein suggesting limited expression of MRP4 in human tissues. Discussion: Elevated MRP4 expression is found in malignant compared to benign prostate tissue while lower MRP4 expression is seen after androgen ablation suggesting that MRP4 may be an androgen-regulated gene. In addition, there is relatively little expression of MRP4 in normal tissues. These data suggest that MRP4 is important in the progression to PC and that it may be a potential therapeutic target. No significant financial relationships to disclose.
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Zhang, Jing, Ka-Yun Ng, and Paul C. Ho. "Interaction of Oxazaphosphorines with Multidrug Resistance-Associated Protein 4 (MRP4)." AAPS Journal 12, no. 3 (April 20, 2010): 300–308. http://dx.doi.org/10.1208/s12248-010-9189-x.

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Hardwick, Rhiannon N., Marina Snellings, Brian C. Ferslew, Yang Lu, and Kim L. R. Browuer. "Tyrosine and aurora kinase inhibitors diminish transport function of multidrug resistance-associated protein (MRP) 4 and breast cancer resistance protein (BCRP)." ADMET and DMPK 4, no. 4 (December 26, 2016): 302. http://dx.doi.org/10.5599/admet.4.4.322.

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<p class="PaperKeywordTitle">Tyrosine and aurora kinases are important effectors in signal transduction pathways that are often involved in aberrant cancer cell growth. Tyrosine (TKI) and aurora (AKI) kinase inhibitors are anti-cancer agents specifically designed to target such signaling pathways through TKI/AKI binding to the ATP-binding pocket of kinases thereby leading to diminished kinase activity. Some TKIs have been identified as inhibitors of ATP-binding cassette (ABC) transporters such as P-glycoprotein and breast cancer resistance protein (BCRP), which are commonly upregulated in malignant cells. TKI/AKIs have been investigated as ABC transporter inhibitors in order to facilitate the accumulation of concomitantly administered chemo-therapeutics within cancer cells. However, ABC transporters are prominently expressed in the liver and other eliminating organs, and their inhibition has been linked to intracellular accumulation of drugs, altered disposition, and toxicity. The potential for TKIs/AKIs to inhibit other important hepatic efflux transporters, particularly multidrug resistance-associated proteins (MRPs), remains unknown. The aim of the current study was to compare the inhibitory potency of 20 selected TKI/AKIs against MRP4 and BCRP through the use of inverted membrane vesicle assays. Relative IC<sub>50 </sub>values were estimated by determining TKI/AKI inhibition of MRP4-mediated [<sup>3</sup>H]-dehydroepiandrosterone sulfate uptake and BCRP-mediated [<sup>3</sup>H]-estrone sulfate uptake. To provide insight to the clinical relevance of TKI/AKI inhibition of ABC efflux transporters, the ratio of the steady-state maximum total plasma concentration (C<sub>ss</sub>) to the IC<sub>50</sub> for each compound was calculated with C<sub>ss</sub>/IC<sub>50</sub> ratio &gt;0.1 deemed potentially clinically relevant. Such analysis identified several potentially clinically relevant inhibitors of MRP4: alisertib, danusertib, erlotinib, lapatinib, neratinib, nilotinib, pazopanib, sorafenib, and tozasertib. The potentially clinically relevant inhibition of BCRP was much more extensive and included alisertib, barasertib, danusertib, enzastaurin, erlotinib, gefitinib, imatinib, neratinib, nilotinib, pazopanib, selumetinib, sorafenib, sunitinib, tozasertib, and vandetanib. These findings indicate the significant potential for TKI/AKIs to inhibit multiple ABC efflux transporters. The resulting inhibition data could provide insight regarding the clinical interpretation of pharmacokinetic/pharmacodynamic outcomes when TKI/AKIs are administered concomitantly with additional chemotherapeutic agents.</p>
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Hayashi, Hisamitsu, Sotaro Naoi, Takayuki Nakagawa, Toru Nishikawa, Hiroyuki Fukuda, Shinobu Imajoh-Ohmi, Ayano Kondo, et al. "Sorting Nexin 27 Interacts with Multidrug Resistance-associated Protein 4 (MRP4) and Mediates Internalization of MRP4." Journal of Biological Chemistry 287, no. 18 (March 12, 2012): 15054–65. http://dx.doi.org/10.1074/jbc.m111.337931.

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Ansari, Marc, Géraldine Sauty, Malgorzata Labuda, Vincent Gagné, Caroline Laverdière, Albert Moghrabi, Daniel Sinnett, and Maja Krajinovic. "Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia." Blood 114, no. 7 (August 13, 2009): 1383–86. http://dx.doi.org/10.1182/blood-2008-11-191098.

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Abstract Methotrexate and 6-mercaptopurine, important components of acute lymphoblastic leukemia treatment, are substrates for multidrug resistance-associated protein MRP4. Eight single nucleotide polymorphisms were analyzed in MRP4 gene, and 4 variants were identified as tagSNPs with frequency more than or equal to 5%. They were investigated for association with treatment responses in 275 children with acute lymphoblastic leukemia. The TC genotype of the regulatory T-1393C polymorphism was associated with better event-free survival (P = .02) and lower methotrexate plasma levels (P = .01). The CA genotype of A934C (Lys304Asn) substitution correlated in contrast with lower event-free survival (P = .02) and higher frequency of high-grade thrombocytopenia (P = .01). Gene reporter assay showed that the promoter haplotype uniquely tagged by the C-1393 allele conferred higher promoter activity compared with remaining haplotypes (P < .001). Further analyses are needed to replicate this pilot study and get closer insight into the functional effect of these polymorphisms.
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May, M., C. Alejandro, N. Gomez, F. Diez, S. Copsel, J. Iturbe, N. Mohr, N. Fernandez, C. Shayo, and C. Davio. "P-020 Targeting multidrug resistance – associated protein 4 (MRP4/ABCC4) in pancreatic cancer." Annals of Oncology 27 (June 2016): ii6. http://dx.doi.org/10.1093/annonc/mdw199.20.

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Sassi, Y., S. El Haou, Y. Fromes, N. Mougenot, G. Vandecasteel, P. Lechat, S. Hatem, A. M. Lompre, and J. S. Hulot. "J016 Inhibition of the multidrug resistance-associated protein 4, MRP4 promotes cardiac hypertrophy." Archives of Cardiovascular Diseases 102 (March 2009): S108. http://dx.doi.org/10.1016/s1875-2136(09)72391-5.

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Dissertations / Theses on the topic "MRP4 (Multidrug Resistance Associated Protein 4)"

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Carillion, Aude. "Physiopathologie de la dysfonction bêta-adrénergique et rôle de la protéine MRP4 au cours du vieillissement, du diabète et du syndrome métabolique." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066485/document.

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Les travaux présentés dans ce mémoire ont pour objectif d’approfondir la compréhension de l’altération de la réponse à la stimulation des récepteurs β-adrénergiques dans plusieurs contextes physiopathologiques. La première étude confirme l’existence d’une dysfonction β-adrénergique à l’échelle du cardiomyocyte au cours de la sénescence. Elle met en lumière le rôle de la protéine MRP4 (multidrug resistance associated protein 4) dans cette diminution de réponse inotrope positive à l’isoprotérénol. La deuxième étude évalue la réponse à la stimulation des récepteurs β-adrénergiques dans le syndrome métabolique et montre que la dysfonction est modérée dans ce contexte même en cas de diabète associé à l’obésité. Ces résultats fonctionnels sont expliqués par la diminution d’expression des récepteurs β1- et β2-adrénergiques mais l’absence de surexpression du récepteur β3-adrénergique comme observée dans le diabète de type 1. La troisième étude analyse le rôle de l’atorvastatine sur la réponse β-adrénergique chez les diabétiques et les mécanismes de modulation de cette réponse par une étude du transcriptome cardiaque. Elle montre également que l’inhibition de la production d’oxyde nitrite améliore la réponse β-adrénergique. La quatrième étude a expliqué une part de la dysfonction β-adrénergique chez les diabétiques par la surexpression de MRP4. L’inhibition de MRP4 a permis de restaurer la réponse à l’isoprotérénol au cours de la cardiopathie diabétique. Au total, l’ensemble de nos travaux poursuit la description des mécanismes de la dysfonction β-adrénergique dans la sénescence et le diabète et souligne le rôle de MRP4
The studies presented in this report looked for a better understanding of the altered response to stimulation of the β-adrenergic receptors in several physiopathological contexts. The first study confirms the alteration of the β-adrenergic response at the cardiomyocyte level in the senescent cardiomyopathy. The role of MRP4 (multidrug resistance associated protein 4) in the reduced inotropic response to isoproterenol is emphasized. The second study evaluates the response to β-adrenoceptors stimulation in the metabolic syndrome and shows mild dysfunction in this context even in obesity associate with diabetes. These functional results are explained by a reduced expression of β1- and β2-adrenergic receptors but no overexpression of β3-adrenoceptor as observed in type 1 diabetes. The third study analyzes the role of atorvastatin on the β-adrenergic response in the diabetic cardiomyopathy and the mechanisms involved by study of the cardiac transcriptome. The inhibition of nitrite oxide production improves the response to β-adrenoceptors stimulation in diabetic heart. The fourth study explained part of the β-adrenergic dysfunction in the diabetic cardiomyopathy by the overexpression of MRP4. The inhibition of this protein restored the response to isoproterenol during diabetic cardiomyopathy. All together the present results carry on with description of the mechanisms involved in the β-adrenergic dysfunction in aging and diabetes and underline the role of MRP4
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Lemaire, Laurine. "Étude des propriétés physico-chimiques de la membrane plasmique comme facteurs modulant l'interaction de molécules et des structures protéiques exogènes." Electronic Thesis or Diss., Compiègne, 2022. http://www.theses.fr/2022COMP2713.

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La membrane plasmique est souvent décrite comme une structure délimitant et protégeant la cellule de son environnement. Son rôle est bien plus complexe et multifonctionnel, c’est une plateforme d’échange et de contact incontournable entre les milieux externes et internes des cellules. De nombreuses fonctions cellulaires lui sont étroitement liées comme la migration, le transport de molécules, certaine voie de signalisation ou le contact avec des micro-organismes. Les travaux de cette thèse se focalisent sur l’étude de processus cellulaires s’orchestrant au niveau membranaire par un système mimant les propriétés des bicouches lipidiques : les liposomes. Ce modèle in vitro, permettant un contrôle fin des conditions expérimentales, représente une alternative aux analyses sur cellules entières souvent peu concluantes, faute de pouvoir cibler suffisamment précisément un processus membranaire en particulier. Les liposomes permettent la focalisation sur une fonction ou un constituant en particulier. Dans cette thèse, l’utilisation du modèle biomimétique a été déclinée pour l’étude de plusieurs processus. Les mécanismes d’adhésion de bactéries flagellées sur les bicouches lipidiques ont été étudiés. Ces informations obtenues sont de haute importance dans le contexte de résistance aux traitements, nous permettant d’avoir plus de données pour le développement de thérapies alternatives aux traitements antibactériens actuels. Le modèle de liposomes a également été utilisé comme base pour la formation de protéoliposomes dans l’étude d’une protéine transmembranaire, MRP4 (multidrug resistance associated protein 4). L’étude de cette protéine constitue un enjeu dans le cadre des traitements multi-médicamenteux car elle est au centre des interactions médicamenteuses. Et enfin, le modèle a été utilisé pour la caractérisation de l’interaction des bicouches de lipides avec des molécules à fort potentiel thérapeutique : les polyphénols. L’ensemble de ces travaux a été réalisé dans le cadre d’une collaboration avec l’équipe du Pr. Patrick Trouillas (Equipe INSERM U1248, CHU de Limoges) qui s’intéresse au développement de modèles cellulaires biomimétiques in silico
The plasma membrane was often described as a structure delimiting and protecting the cell from its external environment. However, his role is much more complex and multifunctional. The membrane is an exchange platform at the cellular external and internal environments. Many cellular functions are closely related to it, such as migration, transport of molecules, some pathways of metabolic signaling, or the contact with micro-organisms. This thesis focuses on the study of some cellular processes occurring at the membrane interface using a system that can mimic the lipid bilayer properties. This membrane models that allow a precise control of the in vitro conditions, represent a good alternative to the often inconclusive studies on whole cells. Liposomes allow focusing on a particular function or constituent. In this thesis, the use of the biomimetic model was declined for the study of several processes. The mechanisms of adhesion of flagellated bacteria to lipid bilayers were studied as a function of the physical properties of the lipid bilayers. This information is of paramount importance in the context of antibiotic resistance, giving more information for the potential development of alternative therapies. The liposome model was also used for forming proteoliposomes to study of a transmembrane protein, MRP4 (multidrug resistance associated protein). The study of this protein is an issue in multi-drug treatments. Indeed, this protein is widely involved in drug interactions. Finally, the liposome model was used to characterize the interaction with lipid bilayers of molecules with high therapeutic potential: polyphenols. All of this work was done in collaboration with the team of the Prof Patrick Trouillas (INSERM U1248 team, Limoges University Hospital) working on the development of biomimetic cell models in silico
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Tan, Kah Poh. "Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities." Thesis, 2008. http://hdl.handle.net/1807/17287.

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Exposure to toxic bile acids (BA) and retinoic acids (RA) is implicated in toxicities related to excessive oxidative stress. This thesis examined roles and mechanisms of the oxidative stress-responsive nuclear factor (erythroid 2-like) factor 2 (Nrf2) in adaptive cell defense against BA and RA toxicities. Using liver cells and mouse models, many antioxidant proteins known to be Nrf2 target genes, particularly the rate-limiting enzyme for glutathione (GSH) biosynthesis, i.e., glutamate-cysteine ligase subunits (GCLM/GCLC), were induced by BA [lithocholic acid (LCA)] or RA (all-trans, 9-cis and 13-cis) treatment. Evidence for increased Nrf2 transactivation by LCA and all-trans-RA was exemplified in HepG2 by: (1) reduced constitutive and inducible expression of GCLM/GCLC upon Nrf2 silencing via small-interfering RNA; (2) increased inducible expression of GCLM/GCLC genes by Nrf2 overexpression, but overexpression of dominant-negative Nrf2 decreased it; (3) increased nuclear accumulation of Nrf2 as signature event of receptor activation; (4) enhanced Nrf2-dependent antioxidant-response-element (ARE) reporter activity as indicative of increased Nrf2 transactivation; and (5) increased Nrf2 occupancy to AREs of GCLM and GCLC. Additionally, in BA-treated HepG2 cells, we observed concomitant increases of many ATP-binding cassette (ABC) transporters (MRPs 1-5, MDR1 and BCRP) in parallel with increased cellular efflux. Nrf2 silencing in HepG2 cells decreased constitutive and inducible expression of MRP2, MRP3 and ABCG2. However, Nrf2-silenced mouse hepatoma cells, Hepa1c1c7, and Nrf2-/- mice had decreased constitutive and/or inducible expression of Mrps 1-4, suggesting species differences in Nrf2-dependent regulation of hepatic ABC transporters. Protection by Nrf2 against BA and RA toxicities was confirmed by observations that Nrf2 silencing increased cell susceptibility to BA- and RA-induced cell death. Moreover, Nrf2-/- mice suffered more severe liver injury than the wildtype. Increased GSH and efflux activity following increased GCLM/GCLC and ABC transporters, respectively, can mitigate LCA toxicity. Activation of MEK1-ERK1/2 MAPK was shown to primarily mediate Nrf2 transactivation and LCA-induced expression of antioxidant proteins and Nrf2-dependent and -independent ABC transporters. In conclusion, Nrf2 activation by BA and RA led to coordinated induction of antioxidant and ABC proteins, thereby counteracting resultant oxidative cytotoxicity. The potential of targeting Nrf2 in management of BA and RA toxicities merits further investigation.
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Conference papers on the topic "MRP4 (Multidrug Resistance Associated Protein 4)"

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Kochel, Tyler, Xinrong Ma, Namita Kundu, Jocelyn Reader, Olga Goloubeva, and Amy M. Fulton. "Abstract 4132: Multiple drug resistance-associated protein 4 (MRP4): Role in triple negative breast cancer." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-4132.

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Leslie, Elaine M., Janet R. Zhou, and Gurnit Kaur. "Arsenic Hepatic Sinusoidal Export is Stimulated by Methylselenocysteine and Mediated by Multidrug Resistance Protein 4 (MRP4/ABCC4)." In ASPET 2023 Annual Meeting Abstracts. American Society for Pharmacology and Experimental Therapeutics, 2023. http://dx.doi.org/10.1124/jpet.122.537850.

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Kochel, Tyler J., Namita Kundu, Xinrong Ma, Jocelyn Reader, and Amy Fulton. "Abstract 2257: Multiple drug resistance-associated protein 4 (MRP4) may contribute to breast cancer metastasis by exporting the COX-2 product PGE2." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2257.

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Kochel, Tyler J., Jocelyn Reader, Namita Kundu, Yanchun Li, Xinrong Ma, Dawn Holt, and Amy Fulton. "Abstract 5119: Multiple drug resistance-associated protein 4 (MRP4) may contribute to breast cancer progression by exporting the COX-2 product PGE2." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-5119.

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