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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  

Cha, Seung Keun (Department of Neuropsychiatry, Seoul National University Hospital)
Kim, Se Hyun (Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University)
Ha, Kyooseob (Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University)
Shin, Soon Young (Department of Biological Sciences, Konkuk University)
Kang, Ung Gu (Department of Neuropsychiatry, Seoul National University Hospital)
Publication Information
Korean Journal of Biological Psychiatry / v.20, no.4, 2013 , pp. 159-165 More about this Journal
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.
Keywords
Mood stabilizers; Mitogen-activated protein kinase; Augmentation; Transcription factors;
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