title: Hypoxia and CoCl2 protect HepG2 cells against serum deprivation- and t-BHP-induced apoptosis: a possible anti-apoptotic role for HIF-1.
abstract: Hypoxia inducible factor-1 (HIF-1) is the main transcriptional factor activated by hypoxia. Besides the well-described role assigned to HIF-1 in the adaptation of cells to hypoxia, different recent data describe a possible role for HIF-1 in the modulation of apoptosis. However, this precise role is not yet clearly understood. In this study, chemical and physiological hypoxia, which were shown to induce HIF-1alpha stabilization and HIF-1 activation, were shown to inhibit apoptosis induced in HepG2 cells by two different pro-apoptotic conditions, serum deprivation- and t-BHP-induced oxidative stress. Indeed, hypoxia reduced DNA fragmentation, caspase activation, and PARP cleavage induced by these two pro-apoptotic conditions. These results are very interesting because it is a clear demonstration that hypoxia and chemical hypoxia have a direct protective effect on apoptotic cell death induced by two different stimuli. This observation is an important data in understanding how tumor growth can occur in challenging environmental conditions.
authors.affiliation: Laboratory of Biochemistry and Cellular Biology, Facultés Universitaires Notre-Dame de la Paix, 5000 Namur, Belgium.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Piret
authors.forename: Christophe
authors.initials: C
authors.lastname: Lecocq
authors.forename: Sebastien
authors.initials: S
authors.lastname: Toffoli
authors.forename: Noelle
authors.initials: N
authors.lastname: Ninane
authors.forename: Martine
authors.initials: M
authors.lastname: Raes
authors.forename: Carine
authors.initials: C
authors.lastname: Michiels
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D003035:Cobalt / Q000633:toxicity*; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D017930:Genes, Reporter; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008113:Liver Neoplasms; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
chemical_list: D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D003035:Cobalt; D020122:tert-Butylhydroperoxide; D020169:Caspases; C018021:cobaltous chloride