Peroxisome proliferator-activated receptor gamma-regulated ABCG2 expression confers cytoprotection to human dendritic cells
| Autor: | Attila Szanto, György Vámosi, Csilla Özvegy-Laczka, Endre Barta, Balint L. Balint, Viktória Jeney, Peter Brazda, József Balla, Szilvia Benko, Istvan Szatmari, Balázs Sarkadi, Lajos Széles, Laszlo Nagy |
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| Rok vydání: | 2006 |
| Předmět: |
animal structures
Abcg2 Cellular differentiation Molecular Sequence Data Peroxisome proliferator-activated receptor Biology Biochemistry Xenobiotics Mice Dogs ATP Binding Cassette Transporter Subfamily G Member 2 Animals Humans Elméleti orvostudományok Enhancer Molecular Biology Transcription factor chemistry.chemical_classification Base Sequence Cell Biology Orvostudományok Dendritic Cells Cytoprotection Cell biology Neoplasm Proteins Up-Regulation PPAR gamma Phenotype Nuclear receptor chemistry Drug Resistance Neoplasm embryonic structures biology.protein ATP-Binding Cassette Transporters Cattle sense organs Stem cell |
| Zdroj: | The Journal of biological chemistry. 281(33) |
| ISSN: | 0021-9258 |
| Popis: | ABCG2, a member of the ATP-binding cassette transporters has been identified as a protective pump against endogenous and exogenous toxic agents. ABCG2 was shown to be expressed at high levels in stem cells and variably regulated during cell differentiation. Here we demonstrate that functional ABCG2 is expressed in human monocyte-derived dendritic cells by the activation of a nuclear hormone receptor, PPARgamma. We identified and characterized a 150-base pair long conserved enhancer region, containing three functional PPAR response elements (PPARE), upstream of the human ABCG2 gene. We confirmed the binding of the PPARgamma x RXR heterodimer to this enhancer region, suggesting that PPARgamma directly regulates the transcription of ABCG2. Consistent with these results, elevated expression of ABCG2 mRNA was coupled to enhanced protein production, resulting in increased xenobiotic extrusion capacity via ABCG2 in PPARgamma-activated cells. Furthermore PPARgamma instructed dendritic cells showed increased Hoechst dye extrusion and resistance to mitoxantrone. Collectively, these results uncovered a mechanism by which up-regulation of functional ABCG2 expression can be achieved via exogenous or endogenous activation of the lipid-activated transcription factor, PPARgamma. The increased expression of the promiscuous ABCG2 transporter can significantly modify the xenobiotic and drug resistance of human myeloid dendritic cells. |
| Databáze: | OpenAIRE |
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