Endogenous reactive oxygen species are essential for proliferation of neural stem/progenitor cells.
It is widely thought that accumulation of reactive oxygen species (ROS) causes injury to cells. In this study, we investigated the effect of endogenous ROS on the proliferation of neural stem/progenitor cells derived from the hippocampus of embryonic mice. The cells were treated with free radical-scavenging agents [3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) or 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol)], an NADPH oxidase inhibitor (apocynin), catalase, a nitric oxide synthase inhibitor [N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME)] or a peroxynitrite generator (SIN-1) during the culture period. Edaravone and tempol had the ability to decrease endogenous ROS in the cells exposed for periods from 1 to 24h, with attenuation of the proliferation activity of the cells during culture. Apocynin and L-NAME were also effective in attenuating cell proliferation but not cellular damage. Conversely, SIN-1 was capable of promoting the proliferation activity. However, catalase had no effect on the proliferation activity of the cells during culture. Furthermore, tempol significantly decreased the level of NFkappaB p65, phospho-cyclic AMP response element-binding protein, and beta-catenin within the nucleus of the cells. These data suggest that endogenous ROS and nitric oxide are essential for the proliferation of embryonic neural stem/progenitor cells.
Yoneyama
Masanori
M
Department of Pharmacology, Setsunan University, Faculty of Pharmaceutical Sciences, Hirakata, Osaka, Japan.
Kawada
Koichi
K
Gotoh
Yuka
Y
Shiba
Tatsuo
T
Ogita
Kiyokazu
K
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000494:pharmacology; D000077553:Edaravone; D053595:Embryonic Stem Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D008297:Male; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D009687:Nuclear Proteins / Q000032:analysis; D017382:Reactive Oxygen Species / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013113:Spin Labels
D000098:Acetophenones; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D013113:Spin Labels; D009569:Nitric Oxide; C002385:linsidomine; C056165:acetovanillone; D008981:Molsidomine; D002374:Catalase; D019255:NADPH Oxidases; D000077553:Edaravone; D000983:Antipyrine; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester