HGF protects cultured cortical neurons against hypoxia/reoxygenation induced cell injury via ERK1/2 and PI-3K/Akt pathways.
Hepatocyte growth factor (HGF) has been revealed to exert multipotent activities on a variety of cells. In this study, we investigated whether HGF had a direct neuroprotection on cultured cerebral cortical neurons subjected to hypoxia/reoxygenation (H/R) and explored the intracellular signalings mediated the effects. The decrease in cell viability and increase in number of apoptotic cells resulting from H/R were significantly prevented by HGF pre-treatment. HGF stimulated both ERK1/2 and Akt activities in cortical neurons. Inhibition of ERK activation completely abolished the protective effects of HGF, and inhibition of Akt activation reduced, but did not completely eliminate the HGF mediated neuroprotection. It is suggested that the neuroprotection of HGF depend on ERK1/2 pathway, and, to a lesser extent, PI-3K/Akt pathway. In addition, we found that pre-treatment with HGF remarkably attenuated the decrease in expression of Bcl-2 and Bcl-xL induced by H/R, but failed to affect the amount of Bax. It is likely that Bcl-2 and Bcl-xL contribute to the protective effects of HGF.
He
Fang
F
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410008, China.
Wu
Li-Xiang
LX
Shu
Kun-Xian
KX
Liu
Fa-Yi
FY
Yang
Li-Juan
LJ
Zhou
Xuan
X
Zhang
Yan
Y
Huang
Bo-Sheng
BS
Huang
Dong
D
Deng
Xiao-Lu
XL
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010100:Oxygen