Hypoxia and CoCl2 protect HepG2 cells against serum deprivation- and t-BHP-induced apoptosis: a possible anti-apoptotic role for HIF-1.
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.
Piret
Jean-Pascal
JP
Laboratory of Biochemistry and Cellular Biology, Facultés Universitaires Notre-Dame de la Paix, 5000 Namur, Belgium.
Lecocq
Christophe
C
Toffoli
Sebastien
S
Ninane
Noelle
N
Raes
Martine
M
Michiels
Carine
C
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*
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