Related Experiment Videos
Increase in AP-1 transcription factor DNA binding activity by valproic acid
1Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Summary
Valproic acid (VPA) enhances activator protein 1 (AP-1) DNA binding activity in brain cells, suggesting a genomic mechanism for its mood-stabilizing effects. This action requires new protein synthesis and may be key to VPA
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Valproic acid (VPA) is clinically effective for manic-depressive illness.
- The precise molecular mechanisms underlying VPA's therapeutic effects are not fully understood.
- VPA's delayed onset and sustained action suggest genomic alterations.
Purpose of the Study:
- To investigate the effects of VPA on the DNA binding activity of transcription factors.
- To explore the role of VPA in modulating gene expression relevant to its therapeutic action.
Main Methods:
- Studied DNA binding activities of activator protein 1 (AP-1) and cAMP responsive element binding protein (CREB).
- Utilized acute and chronic treatment models in rat C6 glioma and human SH-SY5Y neuroblastoma cells.
- Assessed the impact of cycloheximide to determine the requirement for new protein synthesis.
Main Results:
- VPA significantly increased AP-1 DNA binding activity in a concentration- and time-dependent manner.
- AP-1 activity was elevated within 2 hours and sustained for 6 days of VPA treatment.
- VPA did not alter CREB DNA binding activity.
- The VPA-induced increase in AP-1 activity was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis.
Conclusions:
- VPA modulates the DNA binding activity of the transcription factor AP-1.
- This modulation appears to involve the synthesis of new proteins.
- VPA's therapeutic effects in mood disorders may be mediated by altering gene expression through transcription factor regulation.