Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity.
Neuronal apoptosis is a very important event in the development of the central nervous system (CNS), but the underlying mechanisms remain to be elucidated. We have previously shown that safrole oxide, a small molecule, induces integrin beta4 expression and promotes apoptosis in vascular endothelial cells. In this study, the effects of safrole oxide on cell growth and apoptosis have been examined in primary cultures of mouse neurons. Safrole oxide was found to significantly inhibit neuronal cell growth and to induce apoptosis. The inhibitory and apoptotic activities of safrole oxide followed a dose- and time-dependent manner. Interestingly, the expression of integrin beta4 was significantly inhibited with safrole oxide treatment. Furthermore, safrole oxide dramatically increases the level of intracellular reactive oxygen species (ROS) and the activity of NADPH oxidase. Moreover, manganese-dependent superoxide dismutase (MnSOD) activity was decreased significantly with safrole oxide treatment. Our study thus demonstrates that safrole oxide induces neuronal apoptosis through integrin beta4, ROS, NADPH, and MnSOD.
Su
Le
L
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China.
Zhao
BaoXiang
B
Lv
Xin
X
Wang
Nan
N
Zhao
Jing
J
Zhang
ShangLi
S
Miao
JunYing
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D039663:Integrin beta4 / Q000378:metabolism*; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012451:Safrole / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D039663:Integrin beta4; D017382:Reactive Oxygen Species; C009196:safrole oxide; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D012451:Safrole