title: NADPH-cytochrome P450 reductase is regulated by all-trans retinoic acid and by 1,25-dihydroxyvitamin D3 in human acute myeloid leukemia cells.
abstract: Acute myeloid leukemia (AML) cell lines can be driven to differentiate to monocyte-like cells by 1,25- dihydroxyvitamin D3 (1,25D) and to granulocyte-like cells by all-trans-retinoic acid (ATRA). Both compounds activate their specific intracellular receptors, vitamin D receptor (VDR) and retinoic acid receptors (RARs) respectively. Inside the cells 1,25D is degraded to calcitrioic acid by a mitochondrial enzyme CYP24A1, while ATRA is degraded to several polar metabolites by CYP26. NADPH-cytochrome P450 oxidoreductase (POR) is a membrane-bound enzyme required for electron transfer to cytochrome P450 (CYP), vital in the processes of the metabolism of drugs and steroid production in humans. In this paper we report that POR in AML cells, from both cell lines and patients, is upregulated by ATRA and by 1,25D at the level of mRNA and protein. Partial silencing of POR in HL60 cells resulted in augmented differentiation response to 1,25D.
authors.affiliation: Department of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Gocek
authors.affiliation: Department of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Marchwicka
authors.affiliation: Department of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Bujko
authors.affiliation: Department of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Marcinkowska
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D020868:Gene Silencing; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D034741:RNA, Small Interfering; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D014212:Tretinoin; D009251:NADPH-Ferrihemoprotein Reductase