Evidence for Nerve Growth Factor-Potentiating Activities of the Nonpeptidic Compound SR 57746A in PC12 Cells
Autor: | Daniel Caput, Marilyn Magazin, Gérard Le Fur, Anne Pradines, Pascal Schiltz, Pascual Ferrara |
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Rok vydání: | 2002 |
Předmět: |
medicine.medical_specialty
Neurite Cell Survival Pyridines PC12 cell line Protein tyrosine phosphatase Naphthalenes Biology PC12 Cells Biochemistry Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine Neurites Tumor Cells Cultured medicine Animals Actinin Nerve Growth Factors Sodium orthovanadate Cell Differentiation Drug Synergism Genistein Isoflavones Molecular biology Actins Culture Media Rats Endocrinology Nerve growth factor chemistry Cell culture Acetylcholinesterase biology.protein Phosphorylation Serotonin Antagonists Signal Transduction Neurotrophin |
Zdroj: | Journal of Neurochemistry. 64:1954-1964 |
ISSN: | 1471-4159 0022-3042 |
Popis: | SR 57746A (1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride) exhibits neurotrophic activities in vivo and in vitro. We used the rat pheochromocytoma PC12 cell line to investigate in vitro cellular changes induced by SR 57746A. A significant increase in the percentage of cells bearing neurite-like processes was obtained in cells treated by SR 57746A and nerve growth factor (NGF) compared with NGF treatment alone. SR 57746A added alone, however, had no effect on morphogenesis or on survival of cells in serum-free medium. In contrast, SR 57746A induced a "priming" effect on PC12 cells for neurite outgrowth within 6 h of addition of the protein tyrosine kinase inhibitor genistein. An increase in alpha-actinin content resulted from treatment with SR 57746A. Expression of NGF-mediated acetylcholinesterase and choline acetyltransferase was enhanced within 5 days by SR 57746A. The molecule also induced rapid F-actin redistribution. Within 2 min of incubation, outgrowth of F-actin-containing filopodia was clearly visible at the cell periphery, as previously shown with NGF. It is interesting that this effect of SR 57746A could be mimicked by protein tyrosine kinase inhibitors and abolished by preincubation with sodium orthovanadate, a protein tyrosine phosphatase inhibitor. |
Databáze: | OpenAIRE |
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