Role of proton-sensing G protein-coupled receptors on microglial activation and neuronal cell survival in a ischemic situation.

2015 Fiscal Year Final Research Report

• Project/Area Number: 24500435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Gunma University
• Principal Investigator: SATO Koichi 群馬大学, 生体調節研究所, 准教授 (00302498)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: プロトン感知性受容体 / G蛋白共役型受容体 / 脳虚血 / ミクログリア / 脳内炎症 / 炎症性サイトカイン / 細胞死 / 酸性ストレス

Outline of Final Research Achievements

OGR1 family G-protein coupled receptors (GPCR), including OGR1, GPR4, and TDAG8, sense extracellular pH of 8.0-6.0, resulting in the activation of intracellular signaling pathways. Extracellular acidic pH of 6.8-6.1 has been shown to take place with ischemia and neurodegenerative. However, the mechanisms underlying acidic pH-induced actions are poorly understood. This study has especially focused on the roles of proton-sensing GPCR in mouse microglia and neuronal cells in acidic pH cultured medium. Our results suggested that acidic pH inhibits lipopolysaccaride-induced IL-1β production through the TDAG8/cAMP pathway in microglia, and stimulates neuronal NO synthase-mediated cGMP accumulation via OGR1/Ca2+ pathway in N1E115 cells. Thus, the elucidation of the molecular targets for acidic pH actions may provide therapeutic targets of neurodegenerative disorders such as ischemic stroke.

Free Research Field

生化学