Abstract
Lithium inhibits glycogen synthase kinase-3 (GSK-3), which leads to an increase of cytoplasmic beta-catenin levels. In some cell types, but not in others, activated beta-catenin interacts with members of the lymphoid enhancer-binding factor (LEF)/T-cell factor (TCF) family of transcription factors and induces gene expression. Lithium effect on LEF/TCF-mediated gene expression has never been evaluated in cells with a neuronal phenotype. We have constructed a LEF/TCF-dependent luciferase reporter gene to investigate lithium effects on transcription in PC12 cells. In transiently transfected PC12 cells, lithium induced a time-dependent increase in LEF/TCF-mediated luciferase activity. These results are consistent with the known inhibitory effects of lithium on GSK-3 and represent the first demonstration that a LEF/TCF responsive element also mediates lithium-induced gene expression in PC12 cells.
MeSH terms
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Animals
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Antimanic Agents / pharmacology
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Brain / drug effects
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Brain / metabolism
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Brain / physiopathology
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Calcium-Calmodulin-Dependent Protein Kinases / drug effects*
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Size / drug effects
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Cell Size / genetics
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Cytoskeletal Proteins / drug effects*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / drug effects*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Depression / drug therapy
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Depression / metabolism
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Depression / physiopathology
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Energy Metabolism / drug effects
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Energy Metabolism / genetics
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Gene Expression Regulation / drug effects*
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Gene Expression Regulation / physiology
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Genes, Reporter
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Lithium / metabolism*
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Lithium Chloride / pharmacology
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Luciferases / genetics
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Lymphoid Enhancer-Binding Factor 1
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Neurons / drug effects*
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Neurons / metabolism
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PC12 Cells
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Rats
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Trans-Activators*
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Transcription Factors / drug effects*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects*
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Transcription, Genetic / physiology
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Transfection
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beta Catenin
Substances
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Antimanic Agents
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Ctnnb1 protein, rat
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Lymphoid Enhancer-Binding Factor 1
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Trans-Activators
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Transcription Factors
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beta Catenin
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Lithium
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Luciferases
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Glycogen Synthase Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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Lithium Chloride