Hepatocyte growth factor protects human embryonic stem cell derived-neural progenitors from hydrogen peroxide-induced apoptosis.
Promoting human embryonic stem cell (hESC)-derived-neural progenitor survival in the pro-apoptotic niche is pivotal for stem cell replacement therapy. The present study was designed to investigate the protective effect of hepatocyte growth factor (HGF) on hESC-derived neural progenitor injured by hydrogen peroxide (H(2)O(2)) exposure. Treatment of hESC-derived neural progenitor cells with HGF prior to H(2)O(2) exposure conferred protective effect against oxidative stress-induced apoptosis. HGF treatment increased both phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. However, selective inhibition of each pathway supported that the activation of PI3K/AKT, but not ERK1/2, provides survival advantage to the neural progenitor cells. Further investigation indicated that HGF pretreatment could attenuate the decrease of the expression of Bcl-2 protein induced by H(2)O(2), whereas the level of Bax was not affected. Additionally, we observed that H(2)O(2)-induced decrease of mitochondrial transmembrane potential, release of cytochrome c and increase of caspase-3 activation were alleviated by HGF pretreatment. These effects of HGF could be reversed by inhibition of the PI3K/Akt and ERKs pathways, indicating PI3K/Akt and ERKs signaling might be involved in HGF-mediated regulation of mitochondrial apoptotic pathway mediated by H(2)O(2). The neuroprotective effect of HGF might potentially be useful in stem cell-based therapies for neurodegenerative disorders.
Hu
Zhi-Xing
ZX
Dept. of Pharmacology, School of Basic Medical Sciences, Kunming Medical College, Kunming 650500, China.
Geng
Ju-min
JM
Liang
Dao-ming
DM
Luo
Min
M
Li
Ma-Lin
ML
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017228:Hepatocyte Growth Factor; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3