Lithium induces gene expression through lymphoid enhancer-binding factor/T-cell factor responsive element in rat PC12 cells.
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.
Bettini
Ezio
E
Systems Research, GlaxoSmithKline Medicines Research Centre, Via A. Fleming 4, 37135 Verona, Italy. eb25962@gsk.com
Magnani
Enrico
E
Terstappen
Georg C
GC
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D017930:Genes, Reporter; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D008094:Lithium / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D015534:Trans-Activators; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology; D014162:Transfection; D051176:beta Catenin
D018692:Antimanic Agents; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D008094:Lithium; D008156:Luciferases; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride