The effect of gp130 stimulation on glutamate-induced excitotoxicity in primary hippocampal neurons
| Autor: | Jiguang Ge, Yi Sun, Stefan Rose-John, Uwe Otten, Pia März |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty Receptor expression Biophysics Excitotoxicity Glutamic Acid Ciliary neurotrophic factor medicine.disease_cause Hippocampus Biochemistry Antigens CD Cricetinae Internal medicine Cytokine Receptor gp130 medicine Glial cell line-derived neurotrophic factor Animals Humans Ciliary Neurotrophic Factor Rats Wistar Molecular Biology Cells Cultured Neurons Membrane Glycoproteins biology Chemistry Cell Biology Glycoprotein 130 Rats DNA-Binding Proteins Enzyme Activation Endocrinology Trans-Activators biology.protein Ciliary neurotrophic factor receptor CLCF1 Mitogen-Activated Protein Kinases Neurotrophin |
| Zdroj: | Biochemical and Biophysical Research Communications. 295:532-539 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/s0006-291x(02)00706-4 |
| Popis: | Primary hippocampal neurons from newborn rats treated with glutamate showed clear excitotoxicity. This excitotoxicity could be reversed by treatment of the cells with cytokines of the interleukin-6 family. Stimulation of gp130 on hippocampal neurons resulted in tyrosine phosphorylation of STAT3 and activation of p42 and p44 MAP kinases. Receptors for the interleukin-6 type cytokines are active in membrane bound and soluble form. To address the question whether the neurotrophic effect of interleukin-6 type cytokines requires soluble cytokine receptors we used fusion proteins of interleukin-6 coupled to the soluble interleukin-6 receptor and ciliary neurotrophic factor coupled to the soluble ciliary neurotrophic factor receptor. Ciliary neurotrophic factor was as active as the cytokine-receptor fusion protein, indicating that hippocampal neurons express ciliary neurotrophic factor receptor on the cell surface. In contrast, interleukin-6 was only active at very high concentrations whereas the fusion protein of interleukin-6 coupled to the soluble interleukin-6 receptor (Hyper-IL-6) exhibited high neurotrophic activity at the same concentrations as ciliary neurotrophic factor. These data indicate that interleukin-6 receptor expression is very low on hippocampal neurons and that gp130 stimulation can be used to rescue hippocampal neurons from excitotoxicity. |
| Databáze: | OpenAIRE |
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