• Search Research Projects
  • Search Researchers
  1. Back to previous page

Regulation of trascription factor by GABA_B mechanisms in cultured neuronal cells

Research Project

Project/Area Number08672537
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionNihon University

Principal Investigator

ISHIGE Kumiko  Nihon University Pharmacy inst Ins ructor, 薬学部, 助手 (40212873)

Project Period (FY) 1996 – 1997
Project Status Completed(Fiscal Year 1997)
Budget Amount *help
¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1997 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Keywordsgamma-hydoxybutyric acid / cyclic AMP responsive element / activator protein 1 / GABA_B receptors / Ca^<2+> / neuronal cells / activator protein 1 DNA / a ctivator proteinl / 細胞内Ca^<2+>
Research Abstract

It this study, the effect of gamma-hydroxybutyric acid (GHB) in nuclear cyclic AMP responsive element (CRE) -and activator protein 1 (AP-1) DNA-binding activities in primary neuronal cultured cellswas examined. Gel-shift assays showed that exposure of the cells to GHB (1mM) increased nuclear CRE-and AP-1 DNA-binding activities in cultured mouse cerebellar granule cells and cerebral cortical cells. These increases in nuclear DNA-binding activities in cultured mouse cerebellar granule cells were antagonized by specific GABA_B antagonists such as CGP 55845 (1muM) and CGP 35348 (1mM). In addition, treatment of the cells with 1,2-bis (2'-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM), an intracellular Ca^<2+> chelating agent, or thapsigargin, an endoplasmic reticulum Ca^<2+>-ATPase inhibitor, suppressed the GHB-induced increases in nuclear DNA-binding activities. Furthermore, the GHB-induced increases in nuclear CRE-and AP-1 DNA-binding activities were suppressed by treatment with calmodulin kinase II inhibitors such as KN-62 (10muM) and KN-93 (10muM). In addition, the CRE-binding activity was completely supershifted by the CRE-binding protein (CREB) antibody, and was eliminated by the phospholyrated CREB antibody. The AP-1 DNA-binding activity was blocked by c-Jun and c-Fos antibodies. These results siggest that stimulation of GABA_B receptors by GHB activates intracellular Ca2+ storage sites and that increased intracellular Ca^<2+> plays an important role in elevation of nuclear CRE-and AP-1 DNA-binding activities and that calmodulin kinase II plays an important role in DHB-induced increases in both DNA-binding activities in cultured cerebellar granule cells. It is also suggested that GHB promotes the phosphorylation of CREB.

Report

(3results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report

Research Products

(3results)

All Other

All Publications

  • [Publications] 石毛 久美子: "γ-ヒドロキシ酪酸によるマウス小脳顆粒細胞初代培養系のCREBリン酸化におけるカルモジュリンキナーゼIIの役割" 神経化学. 35巻3号. 684-685 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kumiko Ishige, Yoshihisa Ito and Hideomi Fukuda: "Role of calmodulin kinase II in gamma-hydroxybutyric acidinduced CREB phospholyration in cultured mouse cerebellar granule cells" Bulletin of the Japanese Society Neurochemistry. 35. 684-685 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 石毛久美子: "γ-ヒドロキシ酪酸によるマウス小脳顆粒細胞初代培養系のCREBリン酸化におけるカルモジュリンキナーゼIIの役割" 神経化学. 35巻3号. 684-685 (1996)

    • Related Report
      1996 Annual Research Report

URL :

Published : 1996-04-01   Modified : 2016-04-21  

Information FAQ News Terms of Use

Powered by NII kakenhi