Inhibitors of ser/thr phosphatases 1 and 2A induce apoptosis in pituitary GH3 cells
| Autor: | Rüdiger Opitz, Frithjof Tergau, John Marwitz, Hans Jürgen Steinfelder, Iris Quentin, Vera Ritz, J. Weichert, Caroline von Zezschwitz |
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| Rok vydání: | 1997 |
| Předmět: |
Cell Survival
Phosphatase Population Apoptosis DNA Fragmentation In Vitro Techniques Biology Transfection 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Okadaic Acid Phosphoprotein Phosphatases Animals Enzyme Inhibitors Fragmentation (cell biology) Protein kinase A education Oxazoles Cells Cultured 030304 developmental biology Pharmacology 0303 health sciences education.field_of_study L-Lactate Dehydrogenase General Medicine Okadaic acid Molecular biology Rats EGTA chemistry Pituitary Gland 030220 oncology & carcinogenesis DNA fragmentation Marine Toxins Plasmids |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 356:8-16 |
| ISSN: | 0028-1298 |
| DOI: | 10.1007/pl00005032 |
| Popis: | Two structurally different inhibitors of ser/thr phosphatases 1 and 2A, okadaic acid and calyculin A, time- and concentration-dependently stimulated and inhibited cell-specific function (hormone gene expression) in pituitary GH3 cells. The negative effect was associated with the appearance of apoptotic cell death. Nanomolar concentrations of both agents produced the characteristic morphological alterations and a DNA fragmentation ladder. Calyculin A treatment resulted in comparable changes with 10fold lower concentrations than okadaic acid. Observations with derivatives of okadaic acid with no or lower phosphatase inhibitory potency supported the conclusion that apoptosis induction is related to inhibition of ser/thr phosphatases, presumably types 1 and 2A. Membrane damage as measured by lactate dehydrogenase liberation into medium was significantly lower in apoptotic vs. necrotic cells. DNA fragmentation could be reduced by the addition of zinc but not by removal of extracellular calcium with EGTA. Apoptotic changes were reduced by the concomitant activation of protein kinase A by a membrane permeable cAMP analogue. Incubation of cells for 4 months in successively increased concentrations of okadaic acid resulted in a population that proliferated at the initially lethal concentration of 30 nM. |
| Databáze: | OpenAIRE |
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