Insulin-like Growth Factor-I Suppresses Degradation of the Pro-survival Transcription Factor Myocyte Enhancer Factor 2D (MEF2D) During Neuronal Apoptosis
| Autor: | Brent D. Butts, Linseman Da, Tracey A. Laessig, Kim A. Heidenreich, Shoshona S. Le |
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| Rok vydání: | 2003 |
| Předmět: |
Mef2
Programmed cell death Cell Survival Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Hyperphosphorylation chemistry.chemical_element Apoptosis Calcium Biology Transfection Biochemistry Calcium in biology Rats Sprague-Dawley Endocrinology Genes Reporter Cerebellum medicine Animals Insulin-Like Growth Factor I Phosphorylation Transcription factor Cells Cultured Neurons MEF2 Transcription Factors Growth factor Biochemistry (medical) Cytarabine General Medicine Rats Cell biology DNA-Binding Proteins Animals Newborn Myogenic Regulatory Factors chemistry Potassium Protein Processing Post-Translational Signal Transduction Transcription Factors |
| Zdroj: | Hormone and Metabolic Research. 35:763-770 |
| ISSN: | 1439-4286 0018-5043 |
| Popis: | Cultured rat cerebellar granule neurons (CGNs) require depolarization-mediated calcium influx for survival. Calcium regulates the activity of the pro-survival transcription factor, myocyte enhancer factor 2D (MEF2D). MEF2D is hyperphosphorylated and degraded in CGNs undergoing apoptosis induced by lowering the extracellular potassium concentration from 25 mM to 5 mM. Since insulin-like growth factor-I (IGF-I) is known to protect CGNs from apoptotic cell death, we investigated the effects of IGF-I on MEF2D processing during apoptosis. IGF-I administered during the apoptotic insult did not prevent the hyperphosphorylation of MEF2D and consequential loss of DNA binding. However, IGF-I significantly blocked the degradation of MEF2D. Furthermore, IGF-I had no effect on the initial loss of MEF2 transcriptional activity following hyperphosphorylation, but the recovery of MEF2 activity following restoration of intracellular calcium was significantly increased by IGF-I. We conclude that IGF-I blocks the degradation of MEF2D and enhances recovery of MEF2 activity by protecting MEF2D from caspase-dependent cleavage during apoptosis. These results suggest that IGF-I can prolong the time of commitment to irreversible cell death and enhance the recovery of neurons subjected to an acute apoptotic stimulus by preserving the activity of the pro-survival factor MEF2D. |
| Databáze: | OpenAIRE |
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