Respective roles of carbamylcholine and cyclic adenosine monophosphate in their synergistic regulation of cell cycle in thyroid primary cultures
| Autor: | Van Keymeulen, Alexandra, Deleu, Sandrine, Bartek, Jiri, Dumont, Jacques Emile, Roger, Pierre P. |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Cell Cycle Proteins -- physiology
Cell Nucleus -- metabolism Cyclin-Dependent Kinases -- physiology DNA -- biosynthesis Dogs Proto-Oncogene Proteins Mitosis -- drug effects Animals Carbachol -- metabolism Cyclin D3 Cell Cycle -- drug effects Cells Cultured Thyroid Gland -- drug effects Bucladesine -- pharmacology Cell Cycle -- physiology G1 Phase Biologie moléculaire Cyclin-Dependent Kinase 4 Thyroid Gland -- cytology Drug Synergism Hypertrophy Carbachol -- pharmacology Cyclins -- physiology Thyroid Gland -- pathology Cyclic AMP -- physiology Thyroid Gland -- metabolism |
| Zdroj: | Endocrinology, 142 |
| Popis: | The stimulation of thyroid cell proliferation by TSH through cAMP depends on permissive comitogenic factors, generally the insulin-like growth factors and insulin. In dog thyroid primary cultures, the use of the phosphodiesterase-resistant analog of cAMP (Bu)(2)cAMP instead of TSH allowed to unveil a potent comitogenic activity of carbamylcholine, which can substitute for insulin and was shown to mimic insulin action on cell cycle regulatory proteins. Like insulin, carbamylcholine induced the accumulation of cyclin D3 and overcame the repression by cAMP of this protein, which was shown 1) to be essential for cell cycle progression by means of microinjections of a neutralizing antibody; and 2) to be rate limiting for the cAMP-dependent assembly of cyclin D3-cdk4 complexes, their nuclear translocation and the phosphorylation of pRb. Relative to insulin, carbamylcholine offers the significant experimental advantage that its signaling cascades can be immediately deactivated by the muscarinic antagonist atropine. In the presence of carbamylcholine, the elimination of (Bu)(2)cAMP blocked within 2 h the entry of cells into DNA synthesis phase, but the addition of atropine still permitted the entry of cells in S phase. These data support our view that the progression in G1 phase stimulated by cAMP consists of at least two essential actions that are clearly dissociated: in a first stage, depending on the supportive activity of an agent that stimulates the required cyclin D3 accumulation, cAMP induces the assembly and nuclear translocation of cyclin D3-cdk4 complexes, and then cAMP can exert alone the last crucial control that determines the cell commitment toward DNA replication. Journal Article Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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