K-252a and staurosporine promote choline acetyltransferase activity in rat spinal cord cultures
| Autor: | Meyer Sl, J. E. Prantner, Glicksman Marcie A, Forbes Me, Michael E. Lewis, Nicola Neff, Dasgupta M |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Time Factors Cell Survival medicine.medical_treatment Basic fibroblast growth factor Carbazoles Nerve Tissue Proteins Ciliary neurotrophic factor Biochemistry Choline O-Acetyltransferase Indole Alkaloids Cellular and Molecular Neuroscience chemistry.chemical_compound Alkaloids Parasympathetic Nervous System Internal medicine medicine Staurosporine Animals Ciliary Neurotrophic Factor Nerve Growth Factors Protein Kinase Inhibitors Cells Cultured Motor Neurons Neurons biology Growth factor Cell Differentiation Choline acetyltransferase Rats Endocrinology Nerve growth factor chemistry Spinal Cord biology.protein Mitogens Leukemia inhibitory factor medicine.drug Neurotrophin |
| Zdroj: | Journal of neurochemistry. 61(1) |
| ISSN: | 0022-3042 |
| Popis: | The protein kinase inhibitor K-252a increased choline acetyltransferase (ChAT) activity in rat embryonic spinal cord cultures in a dose-dependent manner (EC50 of approximately 100 nM) with maximal stimulatory activity at 300 nM resulting in as much as a fourfold increase. A single application of K-252a completely prevented the marked decline in ChAT activity occurring over a 5-day period following culture initiation. Of 11 kinase inhibitors, only the structurally related inhibitor staurosporine also increased ChAT activity (EC50 of approximately 0.5 nM). Effective concentrations of K-252a were not cytotoxic or mitogenic and did not alter the total protein content of treated cultures. Insulin-like growth factor I, basic fibroblast growth factor, ciliary neurotrophic factor, and leukemia inhibitory factor yielded dose-dependent increases in ChAT activity in spinal cord cultures. The combination of K-252a with insulin-like growth factor-I or basic fibroblast growth factor increased ChAT activity up to eightfold over that of untreated controls, which was greater than that observed with each compound alone. K-252a combined with ciliary neurotrophic factor or leukemia inhibitory factor demonstrated no additive or synergistic effects on ChAT activity. These results suggest that there are multiple mechanisms for the regulation of ChAT activity in spinal cord cultures. The enhancement of spinal cord ChAT activity by K-252a and staurosporine defines a new neurotrophic activity for these small organic molecules and raises the possibility that they may activate some regulatory elements in common with the ciliary neurotrophic factor and leukemia inhibitory factor family of neurotrophic proteins. |
| Databáze: | OpenAIRE |
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