Oct, 1, 2023

Vol.30 No.2, pp. 84-88

Current Issue Archives
Search
Advanced Search
Editorial Office

Review

  • Korean Journal of Biological Psychiatry
  • Volume 20(4); 2013
  • Article

Review

Korean Journal of Biological Psychiatry 2013;20(4):159-65. Published online: Apr, 1, 2013

Abstract PDF Full Text

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

  • Seung Keun Cha, MD1;Se Hyun Kim, MD2;Kyooseob Ha, MD2,3,4;Soon Young Shin*5; and Ung Gu Kang, MD*1,2,4;
    1;Department of Neuropsychiatry, Seoul National University Hospital, Seoul, 2;Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, 3;Department of Neuropsychiatry, Bundang Seoul National University Hospital, Seongnam, 4;Department of Psychiatry and Behavioral Sciences, Seoul National University College of Medicine, Seoul, 5;Department of Biological Sciences, Konkuk University, Seoul, Korea
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.