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001-es BibID:	BIBFORM005097
Első szerző:	Szatmári István (biológus)
Cím:	Peroxisome proliferator-activated receptor gamma-regulated ABCG2 expression confers cytoprotection to human dendritic cells / Szatmari, I., Vamosi, G., Brazda, P., Balint, B. L., Benko, S., Szeles, L., Jeney, V., Ozvegy-Laczka, C., Szanto, A., Barta, E., Balla, J., Sarkadi, B., Nagy, L.
Dátum:	2006
ISSN:	021-9258 (Print)
Megjegyzések:	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.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban agonists Animals antagonists & inhibitors ATP-Binding Cassette Transporters Base Sequence biosynthesis Cattle Cell Differentiation Cells cytology Cytoprotection Dendritic Cells Dogs Drug Resistance Drug Resistance,Neoplasm genetics Human Humans Hungary metabolism Mice Molecular Sequence Data Neoplasm Proteins Phenotype physiology PPAR gamma Proteins Research Support Up-Regulation Xenobiotics
Megjelenés:	The Journal of Biological Chemistry. - 281 : 33 (2006), p. 23812-23823. -
További szerzők:	Vámosi György (1967-) (biofizikus) Brázda Péter (1980-) (biológus, angol-magyar szakfordító) Bálint Bálint László (1971-) (kutató orvos) Benkő Szilvia (1973-) (molekuláris biológus) Széles Lajos (1971-) (molekuláris biológus) Jeney Viktória (1971-) (vegyész, kémia tanár) Özvegy-Laczka Csilla Szántó Attila (1976-) (orvos, biokémikus) Barta Endre (1963-) (molekuláris biológus) Balla József (1959-) (belgyógyász, nephrológus) Sarkadi Balázs Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
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