Phosphorylation of cyclic AMP-response element-binding protein (CREB) is influenced by melatonin treatment in pancreatic rat insulinoma β-cells (INS-1)
| Autor: | Elmar Peschke, Elke Albrecht, Eckhard Mühlbauer, Sabine Wolgast, Ivonne Bazwinsky-Wutschke |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
endocrine system
medicine.medical_specialty IBMX Forskolin biology Pancreatic islets CREB Melatonin receptor Melatonin chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry Downregulation and upregulation Internal medicine biology.protein medicine Luzindole hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Pineal Research. 53:344-357 |
| ISSN: | 0742-3098 |
| DOI: | 10.1111/j.1600-079x.2012.01004.x |
| Popis: | The pineal hormone melatonin exerts its influence on the insulin secretion of pancreatic islets by a variety of signalling pathways. The purpose of the present study was to analyse the impact of melatonin on the phosphorylated transcription factor cAMP-response element-binding protein (pCREB). In pancreatic rat insulinoma β-cells (INS-1), pCREB immunofluorescence intensities in cell nuclei using digitised confocal image analysis were measured to semi-quantify differences in the pCREB immunoreactivity (pCREB-ir) caused by different treatments. Increasing concentrations of forskolin or 3-isobutyl-1-methylxanthine (IBMX) resulted in a dose-dependent rise of the mean fluorescence intensity in pCREB-ir nuclear staining. Concomitant melatonin application significantly decreased pCREB-ir in INS-1 cells after 30-min, 1-hr and 3-hr treatment. The melatonin receptor antagonists luzindole and 4-phenyl-2-propionamidotetraline (4P-PDOT) completely abolished the pCREB phosphorylation-decreasing effect of melatonin, indicating that both melatonin receptor isoforms (MT(1) and MT(2)) are involved. In a transfected INS-1 cell line expressing the human MT(2) receptor, melatonin caused the greatest reduction in pCREB after IBMX treatment compared with nontransfected INS-1 cells, indicating a crucial influence of melatonin receptor density on pCREB regulation. Furthermore, the downregulation of pCREB by melatonin is concomitantly associated with a statistically significant downregulation of Camk2d transcript levels, as measured after 3 hr. In conclusion, the present study provides evidence that the phosphorylation level of CREB is modulated in pancreatic β-cells by melatonin. Mediated via CREB, melatonin regulates the expression of genes that play an important functional role in the regulation of β-cell signalling pathways. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|