Korean J Biol Psychiatry.
2013 Nov;20(4):159-165.
Effects of Combined Treatments of Lithium and Valproate on the Phosphorylation of ERK1/2 and Transcriptional Activity of ELK1 and C-FOS in PC12 Cells
- Affiliations
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- 1Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea. kangug@snu.ac.kr
- 2Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
- 3Department of Neuropsychiatry, Bundang Seoul National University Hospital, Seongnam, Korea.
- 4Department of Psychiatry and Behavioral Sciences, Seoul National University College of Medicine, Seoul, Korea.
- 5Department of Biological Sciences, Konkuk University, Seoul, Korea. shinsy@konkuk.ac.kr
Abstract
OBJECTIVES
Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro.
METHODS
PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay.
RESULTS
Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate.
CONCLUSIONS
Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.
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