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...

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Bibliographic Details
Published in:Experimental cell research 2004-05, Vol.295 (2), p.340-349
Main Authors: Piret, Jean-Pascal, Lecocq, Christophe, Toffoli, Sebastien, Ninane, Noelle, Raes, Martine, Michiels, Carine
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Apoptosis - physiology
Blotting, Western
Carcinoma, Hepatocellular
Caspases - metabolism
Cell Hypoxia - physiology
Cell Line, Tumor
Cobalt - toxicity
Culture Media, Serum-Free
DNA-Binding Proteins - metabolism
Enzyme Activation
Genes, Reporter
Humans
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Liver Neoplasms
Nuclear Proteins - metabolism
Oxidative Stress - drug effects
Oxidative Stress - physiology
Polymerase Chain Reaction
tert-Butylhydroperoxide - pharmacology
Transcription Factors - physiology
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Summary: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.
ISSN:0014-4827
DOI:10.1016/j.yexcr.2004.01.024