Thyroid hormones stabilize acetylcholinesterase mRNA in neuro-2A cells that overexpress the beta 1 thyroid receptor.
We investigated the intracellular events involved in the 3,3',5-triiodo-L-thyronine (T3)-induced accumulation in acetylcholinesterase (AChE) activity in neuroblastoma cells (neuro-2a) that overexpress the human thyroid receptor beta 1 (hTR beta 1). Treatment of these cells with T3 increased AChE activity and its mRNAs after a lag period of 24-48 h, and these levels increased through stabilization of the transcripts by T3. T3 had no effect on the transcriptional rate or processing of AChE transcripts. The protein kinase inhibitor H7 inhibited T3-induced accumulation in AChE activity and its mRNAs, whereas okadaic acid (a potent inhibitor of phosphatases 1 and 2A) potentiated the effect of T3. Okadaic acid and H7 have no effect on the binding of hTR beta 1 to T3 or the transcriptional rate of the AChE gene. Finally, treatment of cells with T3 stimulated cytosolic serine/threonine, but not tyrosine kinase, activities. The time course analysis reveals that the increase in serine/threonine activity precedes the effect of T3 on AChE mRNAs. These results suggest that activation of a serine/threonine protein kinase pathway might be a link between nuclear thyroid hormone receptor activation and stabilization of AChE mRNA.
Department of Medicine and Molecular Biology, CHU Laval Research Center, Ste-Foy, Quebec, Canada.
J
J
Puymirat
P
P
Etongue-Mayer
J H
JH
Dussault
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000096:biosynthesis*; D000818:Animals; D002460:Cell Line; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D009447:Neuroblastoma; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D007546:Isoquinolines; D009281:Naphthalenes; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D014284:Triiodothyronine; D019319:Okadaic Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004004:Dichlororibofuranosylbenzimidazole; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D000110:Acetylcholinesterase; D010749:Phosphoprotein Phosphatases; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate