Hyperphosphorylation of CREB in human dopaminergic neurons: a kinetic study of cellular distribution of total CREB and phospho-CREB following oxidative stress
| Autor: | Richard Stafford, Martyn Howard, S. Sihotra, Kunjan K. Patel, Bushra Y. Ahmed, Omair Husnain, Abhay S. Gujar, Vimal Moradiya |
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| Rok vydání: | 2013 |
| Předmět: |
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Western Hyperphosphorylation Nerve Tissue Proteins Mitochondrion CREB medicine.disease_cause Cell Line Mitochondrial Proteins Hydroxydopamines Cytosol Neural Stem Cells CREB in cognition medicine Humans Phosphorylation Cyclic AMP Response Element-Binding Protein Cell Nucleus biology Chemistry General Neuroscience Dopaminergic Neurons Parkinson Disease Cell biology DNA-Binding Proteins Kinetics Oxidative Stress Data Interpretation Statistical Cancer research biology.protein Signal transduction Oxidative stress |
| Zdroj: | Neuroreport. 24(13) |
| ISSN: | 1473-558X |
| Popis: | The neurotoxin, 6-hydroxy dopamine (6-OHDA)-induced oxidative stress causes alterations in intracellular signalling events and activates cellular and molecular mechanisms leading to the degeneration of the dopamine-containing neurons (DCNs). The cyclic-AMP response element-binding protein (CREB) modulates the transcription of mitochondrial and nuclear genes upon phosphorylation. However, oxidative stress disrupts CREB functions and inhibits CREB signalling pathways. We have measured the activities and levels of both total CREB and its phosphorylated form (phospho-CREB) in cytosolic, mitochondrial and nuclear compartments in control (untreated) and stressed (6-OHDA-treated) DCN, differentiated from the ReNVM cell line (dDCN) at 0, 24 and 72 h time points following oxidative stress. Our results indicate that CREB phosphorylation occurs in all three subcellular locations. It further shows significant disruption of the phosphorylation process by 6-OHDA treatment and shows tridirectional trafficking of total CREB and phospho-CREB between cytosol, mitochondria and nucleus following oxidative stress induced by 6-OHDA treatment. In conclusion, our results indicate the presence of specific signalling molecules in all the compartments studied and their involvement in the signal transduction processes, where total CREB and phospho-CREB levels and activities are either upregulated or downregulated to balance each other for their roles. |
| Databáze: | OpenAIRE |
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