Lithium induces gene expression through lymphoid enhancer-binding factor/T-cell factor responsive element in rat PC12 cells

• Published in: Neuroscience letters Vol. 317; no. 1; pp. 50 - 52
• Main Authors: Bettini, Ezio, Magnani, Enrico, Terstappen, Georg C.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 04-01-2002; Elsevier
• Subjects: Animals; Antimanic Agents - pharmacology; beta Catenin; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Calcium-Calmodulin-Dependent Protein Kinases - drug effects; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell Size - drug effects; Cell Size - genetics; Cytoskeletal Proteins - drug effects; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Depression - drug therapy; Depression - metabolism; Depression - physiopathology; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Energy Metabolism - drug effects; Energy Metabolism - genetics; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Genes, Reporter; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; Lithium; Lithium - metabolism; Lithium Chloride - pharmacology; Luciferase; Luciferases - genetics; Lymphoid enhancer-binding factor; Lymphoid Enhancer-Binding Factor 1; Medical sciences; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; PC12; PC12 Cells; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Reporter gene; T-cell factor; Trans-Activators; Transcription Factors - drug effects; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - drug effects; Transcription, Genetic - physiology; Transfection; PC12; Reporter gene; Luciferase; T-cell factor; Lithium; Gene expression; Lymphoid enhancer-binding factor; Rat; Psychotropic; Rodentia; Response element; In vitro; Vertebrata; Mammalia; Cell line; Neuron; Mood stabilizer; Animal; Transcription factor
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)02405-3

Lithium inhibits glycogen synthase kinase-3 (GSK-3), which leads to an increase of cytoplasmic β-catenin levels. In some cell types, but not in others, activated β-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.