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.
- Author:
Seung Keun CHA
1
;
Se Hyun KIM
;
Kyooseob HA
;
Soon Young SHIN
;
Ung Gu KANG
Author Information
1. Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea. kangug@snu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Mood stabilizers;
Mitogen-activated protein kinase;
Augmentation;
Transcription factors
- MeSH:
Animals;
Genes, Reporter;
Humans;
Lithium Chloride;
Lithium*;
PC12 Cells*;
Pheochromocytoma;
Phosphorylation*;
Phosphotransferases;
Signal Transduction;
Transcription Factors;
Valproic Acid*
- From:Journal of the Korean Society of Biological Psychiatry
2013;20(4):159-165
- CountryRepublic of Korea
- Language:Korean
-
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.
