ORBi: Piret Jean-Pascal - Hypoxia-inducible Factor-1-dependent Overexpression of Myeloid Cell Factor-1 Protects Hypoxic Cells against tert-Butyl Hydroperoxide-induced Apoptosis

Reference : Hypoxia-inducible Factor-1-dependent Overexpression of Myeloid Cell Factor-1 Protects Hy...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology
	To cite this reference:	http://hdl.handle.net/2268/84907

Title :	Hypoxia-inducible Factor-1-dependent Overexpression of Myeloid Cell Factor-1 Protects Hypoxic Cells against tert-Butyl Hydroperoxide-induced Apoptosis
Language :	English
Author, co-author :	Piret, Jean-Pascal [ > > ]
	Minet, Emmanuel [ > > ]
	Cosse, Jean-Philippe [Université de Liège - ULg > > GIGA-R : Epigénétique Cellulaire et Moléculaire >]
	Ninane, Noelle [ > > ]
	Debacq, Christophe [ > > ]
	Raes, Martine [ > > ]
	Michiels, Carine [ > > ]
Publication date :	Mar-2005
Journal title :	Journal of Biological Chemistry
Publisher :	American Society for Biochemistry and Molecular Biology
Volume :	280
Pages :	9336
Peer reviewed :	Yes (verified by ORBi)
Audience :	International
ISSN :	0021-9258
e-ISSN :	1083-351X
City :	Baltimore
Country :	MD
Keywords :	[en] Hypoxia ; apoptosis ; Mcl-1 ; HIF-1
Abstract :	[en] Increased levels of Mcl-1 (myeloid cell factor-1) have been reported in several cancers, suggesting an important role played by Mcl-1 in cancer cell survival. Mcl-1 is an anti-apoptotic protein shown to delay or block apoptosis. In this work, using semiquantitative immunofluorescence, real-time PCR, and RNase protection assay, an increase in Mcl-1 expression was detected in hepatoma HepG2 cells incubated under hypoxia or in the presence of cobalt chloride. Through analysis of the Mcl-1 promoter sequence, a putative HIF-1 (hypoxiainducible factor-1) binding site was identified. A Mcl-1 promoter fragment containing this hypoxia-responsive element was able to bind HIF-1 in vitro. It also induced hypoxia-dependent transcription of a luciferase reporter gene, which was suppressed by anti-HIF-1 short interfering RNA. Finally, overexpression of Mcl-1 protected HepG2 cells against apoptosis induced by tertbutyl hydroperoxide as shown by inhibition of caspase-3 activation and DNA fragmentation. All these data suggest a potential anti-apoptotic role of HIF-1 that could protect cells against apoptosis under hypoxia by overexpression of the Mcl-1 protein.
Research units :	Unité de Recherche en Biologie Cellulaire
Funders :	Facultés Universitaires Notre-Dame de La Paix
Target :	Researchers
Permalink :	http://hdl.handle.net/2268/84907
DOI :	10.1074/jbc.M411858200

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