CRHR1 mediates p53 transcription induced by high altitude hypoxia through ERK 1/2 signaling in rat hepatic cells
| Autor: | Ming-Yang Wang, Ji-Zeng Du, Xue-Qun Chen, Ke Hao, Yang Zhao |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Transcriptional Activation MAPK/ERK pathway Transcription Genetic MAP Kinase Signaling System Physiology Receptors Corticotropin-Releasing Hormone Biochemistry Cell Line Rats Sprague-Dawley Cellular and Molecular Neuroscience Transactivation Endocrinology Downregulation and upregulation Gene expression medicine Animals RNA Messenger Hypoxia Receptor Chemistry Altitude Hypoxia (medical) Molecular biology Cell Hypoxia Rats Liver Apoptosis Hepatocytes Hepatic stellate cell Tumor Suppressor Protein p53 medicine.symptom |
| Zdroj: | Peptides. 44:8-14 |
| ISSN: | 0196-9781 |
| DOI: | 10.1016/j.peptides.2013.03.023 |
| Popis: | We have previously reported that hypoxia activates corticotrophin-releasing hormone (CRH) and the expression of its type-1 receptor (CRHR1) and induces disorders of the brain-endocrine-immune network. p53 is activated by hypoxia and involved in tumorigenesis and apoptosis. Whether CRHR1 regulates p53 transactivation to further influence apoptotic genes remains unclear. Here, we showed that hypoxia at a simulated altitude of 5km or 7km for 8 and 24h increased p53 protein and mRNA, and reduced apoptotic bax and IGFBP3 gene expression while upregulating the cell-arrest gene p21 for 8h in rat liver cells. The upregulation of p53 mRNA and downregulation of bax mRNA induced by hypoxia were blocked by pretreatment with the specific CRHR1 antagonist CP-154,526, but the downregulation of IGFBP3 and upregulation of p21 mRNA were not. Furthermore, CRH stimulated p53 mRNA via the ERK 1/2 pathway in the BRL-3A cell line and this was blocked by the ERK 1/2 antagonist U0126. These data provide novel evidence that the CRHR1-triggered ERK 1/2 pathway is involved in the activation of p53 and suppression of the apoptotic bax gene by hypoxia in rat liver. |
| Databáze: | OpenAIRE |
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