CREB Negatively Regulates IGF2R Gene Expression and Downstream Pathways to Inhibit Hypoxia-Induced H9c2 Cardiomyoblast Cell Death
| Autor: | Hsin Nung Chang, Chih Yang Huang, Peiying Pai, Wei Wen Kuo, Tsung Jung Ho, Wei-Kung Chen, Vijaya Padma Viswanadha, Dennis Jine Yuan Hsieh, Kuan Ho Lin, Lung Fa Pan |
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| Rok vydání: | 2015 |
| Předmět: |
p300-CBP coactivator family
Cell Survival CREB hypoxia apoptosis IGF2R signaling Catalysis Receptor IGF Type 2 Article Cell Line lcsh:Chemistry Inorganic Chemistry chemistry.chemical_compound CREB in cognition Humans Cyclic adenosine monophosphate Electrophoretic mobility shift assay Myocytes Cardiac Physical and Theoretical Chemistry Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic lcsh:QH301-705.5 Molecular Biology Transcription factor Spectroscopy Regulation of gene expression biology Organic Chemistry General Medicine Molecular biology Computer Science Applications Protein Transport lcsh:Biology (General) lcsh:QD1-999 chemistry Gene Expression Regulation biology.protein Signal transduction Protein Binding Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 16, Iss 11, Pp 27921-27930 (2015) Volume 16 Issue 11 Pages 27921-27930 International Journal of Molecular Sciences; Volume 16; Issue 11; Pages: 27921-27930 |
| ISSN: | 1422-0067 |
| Popis: | During hypoxia, gene expression is altered by various transcription factors. Insulin-like growth factor-II (IGF2) is known to be induced by hypoxia, which binds to IGF2 receptor IGF2R that acts like a G protein-coupled receptor, might cause pathological hypertrophy or activation of the mitochondria-mediated apoptosis pathway. Cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB) is central to second messenger-regulated transcription and plays a critical role in the cardiomyocyte survival pathway. In this study, we found that IGF2R level was enhanced in H9c2 cardiomyoblasts exposed to hypoxia in a time-dependent manner but was down-regulated by CREB expression. The over-expression of CREB in H9c2 cardiomyoblasts suppressed the induction of hypoxia-induced IGF2R expression levels and reduced cell apoptosis. Gel shift assay results further indicated that CREB binds to the promoter sequence of IGF2R. With a luciferase assay method, we further observed that CREB represses IGF2R promoter activity. These results suggest that CREB plays an important role in the inhibition of IGF2R expression by binding to the IGF2R promoter and further suppresses H9c2 cardiomyoblast cell apoptosis induced by IGF2R signaling under hypoxic conditions. |
| Databáze: | OpenAIRE |
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