Characterization of H2O2-induced acute apoptosis in cultured neural stem/progenitor cells.
In the present study, we characterized hydrogen peroxide (H2O2)-induced cell apoptosis and related cell signaling pathways in cultured embryonic neural stem/progenitor cells (NS/PCs). Our data indicated that H2O2 induced acute cell apoptosis in NS/PC in concentration- and time-dependent manners and selectively, it transiently increased PI3K-Akt and Mek-Erk1/2 in a dose-dependent manner. Inhibition of PI3K-Akt with wortmannin, a PI3-K inhibitor, was found to significantly increase H2O2-induced acute apoptosis and dramatically decrease basal pGSK3beta levels. The level of pGSK3beta remained unchanged with H2O2 exposure. We conclude that the transient activation of PI3K-Akt signaling delays the H2O2-induced acute apoptosis in cultured NS/PCs in part through maintaining the basal pGSK3beta level and activating other downstream effectors.
Lin
Hsingchi J
HJ
Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington, DC 20375, USA. jlin@cbmse.nrl.navy.mil
Wang
Xiantao
X
Shaffer
Kara M
KM
Sasaki
Carl Y
CY
Ma
Wu
W
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000196:embryology; D016923:Cell Death; D053938:DNA Fragmentation; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D010766:Phosphorylation; D011419:Propidium / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000473:pathology*; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D011518:Proto-Oncogene Proteins; D011419:Propidium; D006861:Hydrogen Peroxide; C494920:Akt1 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; C007740:fluorexon; D000077191:Wortmannin