Hypoxia-inducible Factor-1-dependent Overexpression of Myeloid Cell Factor-1 Protects Hypoxic Cells against tert-Butyl Hydroperoxide-induced Apoptosis
| Autor: | Jean-Pascal Piret, Martine Raes, Christophe Debacq, Carine Michiels, Emmanuel Minet, Noelle Ninane, Jean-Philippe Cosse |
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| Rok vydání: | 2005 |
| Předmět: |
Small interfering RNA
Carcinoma Hepatocellular DNA Complementary Cell Apoptosis Biology Polymerase Chain Reaction Biochemistry tert-Butylhydroperoxide Transcription (biology) Cell Line Tumor hemic and lymphatic diseases medicine Humans RNA Small Interfering Binding site Molecular Biology DNA Primers Liver Neoplasms Nuclear Proteins Nuclease protection assay Cell Biology Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Neoplasm Proteins DNA-Binding Proteins Gene Expression Regulation Neoplastic medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Cancer cell Myeloid Cell Leukemia Sequence 1 Protein DNA fragmentation Hypoxia-Inducible Factor 1 Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 280:9336-9344 |
| ISSN: | 0021-9258 |
| Popis: | 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-1alpha short interfering RNA. Finally, overexpression of Mcl-1 protected HepG2 cells against apoptosis induced by tert-butyl 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. |
| Databáze: | OpenAIRE |
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