Abstract
Choline-O-acetyltransferase (ChAT) is the enzyme which catalyses the biosynthesis of the neurotransmitter acetylcholine in cholinergic neurons. Here we show that in mouse cholinergic NS-20Y neuroblastoma cells cultured in the presence of either okadaic acid (serine/threonine phosphatases 1 and 2A inhibitor) or KN-62 (CaM kinase inhibitor) ChAT activity and mRNA either increased or decreased as a function of the drug concentration, respectively. After 24 h exposure, okadaic acid exerted a dramatic effect on cell morphology; cells became round and had no more neurites. On the contrary, KN-62 induced a slight morphological differentiation of the cells. The present results suggest that phosphatases 1 and 2A and CaM kinase could mediate regulation of ChAT gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Choline O-Acetyltransferase / biosynthesis*
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Choline O-Acetyltransferase / genetics
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Enzyme Induction / drug effects
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Enzyme Inhibitors / pharmacology*
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Gene Expression Regulation, Neoplastic / drug effects*
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Mice
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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Neuroblastoma / enzymology
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Neuroblastoma / pathology*
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Okadaic Acid / pharmacology*
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphoprotein Phosphatases / physiology*
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / enzymology
Substances
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Enzyme Inhibitors
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Okadaic Acid
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KN 62
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Choline O-Acetyltransferase
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Calcium-Calmodulin-Dependent Protein Kinases
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Phosphoprotein Phosphatases