Disease relevance of Abcb1b

• These studies demonstrate that, in murine erythroleukemia cells selected for vincristine resistance, overexpression of murine mrp occurred prior to that for murine mdr [1].
• Suppression of intestinal polyposis in Mdr1-deficient ApcMin/+ mice [2].
• We show that the expression of mdr1 is increased at the transcriptional level upon treatment of the hepatoma cell line Hepa-1c1c7 with the polycyclic aromatic hydrocarbon 3-methylcholanthrene (3-MC) [3].
• Multidrug resistance gene 1 expression in salivary gland adenocarcinomas and oral squamous-cell carcinomas [4].
• Tet was an extremely potent MDR modulator both in vitro and in vivo, without apparently enhancing the toxicity of the co-administered drugs [5].

Psychiatry related information on Abcb1b

• Furthermore, the mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO mice remains to be elucidated [6].

High impact information on Abcb1b

• The complete nucleotide and primary structure (1276 amino acids) of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented [7].
• The deduced amino acid sequence suggests that mdr is a membrane glycoprotein which includes six pairs of transmembrane domains and a cluster of potentially N-linked glycosylation sites near the amino terminus [7].
• In these cell lines high levels of resistance are frequently associated with amplification and overexpression of a small group of genes termed mdr or gp170 [8].
• Our results demonstrate that overexpression of a single member of the mdr group is sufficient to confer drug resistance [8].
• Our results indicate that specific inhibitors of MRP1 used to reverse MDR, in combination with carcinostatic drugs transported by MRP1, might lead to drug-induced mucositis, (temporary) infertility, and diabetes insipidus [9].

Chemical compound and disease context of Abcb1b

• In mice bearing the MDR MCF-7/adr cell xenografts, coadministration of Tet potentiated the antitumour activity of doxorubicin without a significant increase in toxicity [5].
• Pivotal phase III trials to test these concepts with PSC 833 as an MDR modulator are under way or planned for patients with acute myeloid leukemias, multiple myeloma, and ovarian carcinoma [10].
• Some known anticancer medicines such as platidiam, novantron, fluorouracil, bleomycin and methotrexate were ineffective/while vinca alkaloids exerted a strong reversal effect on the mdr of lymphoma cells [11].
• The mdr-gene expression of the mouse lymphoma cells (which were transfected with the human mdr-1 gene) could be reduced by phenothiazines such as promethazine and trifluoperazine, when the cells were cultured in the presence of 0.5 microgram/mL phenothiazines [11].
• The ability of piceatannol (1) and the three methylated derivatives to modulate the transport activity of P-glycoprotein (P-gp) and apoptosis induction on the L5178 mouse lymphoma cell line containing the human MDR1 gene was studied by flow cytometry [12].

Biological context of Abcb1b

• We hypothesized that there are changes in placental Abcb1a and Abcb1b gene expression and ABCB1 protein levels during pregnancy [13].
• In conclusion, there are dramatic decreases in Abcb1a and Abcb1b mRNA and in ABCB1 at the maternal-fetal interface over the second half of gestation, suggesting that the fetus may become increasingly susceptible to the influences of xenobiotics and natural steroids in the maternal circulation [13].
• In individual cell lines showing gene amplification, the copy number of each of the three mdr genes was identical, suggesting that the three mdr genes became amplified as part of a single amplicon in these cells [14].
• Nucleotide and predicted amino acid sequence analyses showed that the three mouse mdr genes encode highly homologous membrane glycoproteins, which share the same length (1,276 residues), the same predicted functional domains, and overall structural arrangement [15].
• Sequence comparison indicated that the three mouse mdr genes were created from a common ancestor by two independent gene duplication events, the most recent one producing mdr1 and mdr3 [15].

Anatomical context of Abcb1b

• Abcb1b mRNA was detected in invading trophoblast cells by E9.5, peaked within the placental labyrinth at E12.5, and then progressively decreased toward term (P < 0.0001) [13].
• Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier [16].
• It was recently shown that naturally occurring Mdr1a mutant fetuses of the CF-1 outbred mouse stock have no placental Mdr1a P-glycoprotein (P-gp) and that this absence is associated with increased sensitivity to avermectin, a teratogenic pesticide [17].
• Southern blotting analyses of genomic DNA from a panel of independently derived multidrug-resistant cell lines identified mdr gene amplification in 10 of 12 cell lines studied [14].
• Expression, up-regulation, and transport activity of the multidrug-resistance protein Abcg2 at the mouse blood-brain barrier [18].

Associations of Abcb1b with chemical compounds

• A strong correlation existed between placental Abcb1b mRNA and maternal progesterone concentrations, indicating a potential role of progesterone in regulation of placental Abcb1b mRNA [13].
• Thus, this paper provides insight into the mechanisms of glucocorticoid transport in cells and demonstrates a diversity of two independent mechanisms of transport of glucocorticoids by Abcb1a/Abcb1b and Abcc1a with individual patterns of steroid specificity [19].
• Herein, we report that living cells stably transfected with a codon-humanized Rluc show coelenterazine-mediated bioluminescence in a highly MDR1 Pgp-modulated manner [20].
• Photolabelling experiments indicate that Mdr3 synthesized in yeast cells binds the drug analog [125I]iodoaryl azidoprazosin, this binding being competed for by vinblastine and tetraphenylphosphonium bromide, two known multidrug resistance drugs [21].
• The ability of the anticancer drug and potent genotoxic agent daunorubicin to induce mdr1 independently of AhR.Arnt further supports the proposition that mdr1 is transcriptionally up-regulated by p53 in response to DNA damage [3].

Physical interactions of Abcb1b

• Labeling experiments using membrane-enriched fractions and a photoactivatable analogue of ATP showed that the Mdr2 protein was properly inserted in the membrane of transfected cells and could bind this ligand with an apparent affinity similar to that of Mdr1 [22].
• 3-MC treatment of the cells increased the levels of p53 and induced p53 binding to the mdr1 promoter in an AhR.Arnt-dependent manner [3].
• MDR phenotype of these cells is connected with increased levels and activities of p38-MAPK [23].

Regulatory relationships of Abcb1b

• Benzo(a)pyrene, a polycyclic aromatic hydrocarbon and AhR ligand, which, like 3-MC, is oxidized by metabolizing enzymes regulated by AhR.Arnt, also activated p53 and induced mdr1 transcription [3].
• An analysis of promoter methylation in MDR cell lines demonstrated that this mechanism may play a role in regulating the transcription of mdr2, but not of mdr1b [24].
• Furthermore, PD-98059 and U0126, two MAPK inhibitors, blocked PLC-gamma 1-induced expression of MDR1 [25].

Other interactions of Abcb1b

• We report the cloning and functional analysis of a complete clone for the third member of the mouse mdr gene family, mdr3 [15].
• 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 [26].
• The inability of the mouse mdr2 gene to confer multidrug resistance is linked to reduced drug binding to the protein [22].
• Aromatic hydrocarbon receptor (AhR).AhR nuclear translocator- and p53-mediated induction of the murine multidrug resistance mdr1 gene by 3-methylcholanthrene and benzo(a)pyrene in hepatoma cells [3].
• In contrast to results in mice housed in Amsterdam, in the genetically identical mdr1a or mdr1a/1b (-/-) male mice housed in the United States, hepatic P-450 expression was unaffected by mdr1 genotype or actually showed a slight decrease in mdr1a (-/-) mice [27].

Analytical, diagnostic and therapeutic context of Abcb1b

• Using in situ hybridization, we demonstrated that Abcb1b mRNA is the predominant placental isoform and that there are profound gestational changes in the expression of both Abcb1a and Abcb1b mRNA [13].
• The expression of murine mdr genes, as analyzed by Northern blotting, revealed a baseline expression of murine mdr2 in parental cells that was unchanged in the drug-resistant cell lines [1].
• Western blot analysis showed that the three antibodies could discriminate between the three isoforms in membrane fractions from Hamster cells transfected with the corresponding full-length or chimeric mdr cDNAs [28].
• Sequence analyses of mdr cDNAs predict a protein formed by two symmetrical halves, each composed of six transmembrane (TM) segments and one ATP-binding domain [29].
• Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumours [5].

References