Lithium attenuates nerve growth factor-induced activation of AP-1 DNA binding activity in PC12 cells.
This investigation tested if lithium, the primary therapeutic agent for bipolar mood disorder, modulated activation of the AP-1 transcription factor in PC12 cells treated with nerve growth factor (NGF), which induces robust responses in these cells. NGF induced large, time-dependent increases in AP-1 DNA binding activity. Pretreatment with 5 mmol/L lithium for 24 h reduced AP-1 induction by NGF by 42%; shorter treatments and lower concentrations of lithium had smaller inhibitory effects on AP-1. This effect of lithium was not limited to AP-1, as it also inhibited NGF-induced cyclic AMP responsive element (CRE) DNA binding activity. In contrast, activation of AP-1 and CRE by forskolin was unaffected by lithium. AP-1 constituent proteins were differentially susceptible to lithium, as cJun was reduced by 55%, cFos was unaffected by lithium, and an intermediate effect was observed with Jun B. These results reveal that lithium modulates the activation of transcription factors in a neuronal cell model, indicating that selective regulation of gene expression may contribute to the long term in vivo effect of lithium.
Unlap
M T
MT
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham 35294-0017, USA.
Jope
R S
RS
D051698:Activating Transcription Factor 2; D000818:Animals; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004336:Drug Antagonism; D018021:Lithium Chloride / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D009414:Nerve Growth Factors; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D005576:Colforsin; D004247:DNA; D018021:Lithium Chloride