Artigo Revisado por pares

Hepatocyte growth factor protects cultured rat cerebellar granule neurons from apoptosis via the phosphatidylinositol-3 kinase/Akt pathway

2000; Wiley; Volume: 59; Issue: 4 Linguagem: Inglês

10.1002/(sici)1097-4547(20000215)59

ISSN

1097-4547

Autores

Lilin Zhang, Toshiyuki Himi, Ikuo Morita, Sei‐itsu Murota,

Tópico(s)

Cell death mechanisms and regulation

Resumo

Journal of Neuroscience ResearchVolume 59, Issue 4 p. 489-496 Hepatocyte growth factor protects cultured rat cerebellar granule neurons from apoptosis via the phosphatidylinositol-3 kinase/Akt pathway LiLin Zhang, Corresponding Author LiLin Zhang [email protected] Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanDepartment of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, JapanSearch for more papers by this authorToshiyuki Himi, Toshiyuki Himi Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanSearch for more papers by this authorIkuo Morita, Ikuo Morita Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanSearch for more papers by this authorSei-itsu Murota, Sei-itsu Murota Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanSearch for more papers by this author LiLin Zhang, Corresponding Author LiLin Zhang [email protected] Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanDepartment of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, JapanSearch for more papers by this authorToshiyuki Himi, Toshiyuki Himi Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanSearch for more papers by this authorIkuo Morita, Ikuo Morita Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanSearch for more papers by this authorSei-itsu Murota, Sei-itsu Murota Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, JapanSearch for more papers by this author First published: 14 February 2000 https://doi.org/10.1002/(SICI)1097-4547(20000215)59:4 3.0.CO;2-9Citations: 57AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Recent studies suggest that hepatocyte growth factor (HGF) functions as a neurotrophic factor in the central nervous system. In this study, we investigated the neuroprotective effect of HGF and its mechanism of action. We used cultured cerebellar granule neurons that underwent apoptosis when the culture medium was changed from that containing serum with 25 mM K+ to serum-free medium containing 5 mM K+, and HGF prevented apoptotic cell death. HGF stimulated both mitogen-activated protein (MAP) kinase and phosphatidylinositol-3 (PI3)-kinase activity in cerebellar granule neurons. Two specific inhibitors of PI3-kinase, wortmannin and LY294002, efficiently blocked this neuroprotective effect of HGF. In contrast, PD98059, a selective inhibitor of MAP kinase kinase (MEK), did not affect the anti-apoptotic effect of HGF. The downstream signal of PI3-kinase in this protection was further investigated. 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