Survivin is involved in the anti-apoptotic effect of edaravone in PC12 cells.
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a newly developed hydroxy radical scavaging agent which has been widely used for protection against ischemia-reperfusion injury is highly effective in preventing cell apoptosis. However, the exact intracellular mechanism(s) underlying the protective action of edaravone is not clear. We observed that in PC12 cells cultured under serum deprivation (DEPV) condition, the levels of survivin were positively correlated with the anti-apoptotic action of edaravone. Survivin RNA interference (RNAi) increased DEPV-induced PC12 cell apoptosis, whereas the anti-apoptotic effect of edaravone was blunted by survivin RNAi. Moreover, survivin overexpression provided protection against DEPV-induced PC12 cell apoptosis. Inhibition of ERK and PI(3)-K/AKT prevented edaravone's ability to decrease apoptosis and increase survivin. In conclusion, the present study provides the first direct evidence that survivin involves in the anti-apoptotic effects of edaravone via a pathway involving ERK and PI(3)-K/AKT.
Liu
Xue-Yuan
XY
Neurology Department, ShangHai Tenth People Hospital Affiliated to Tongji University, 301 Yan Chang Middle Road, Shanghai 200072, China.
Yao
Ling-Ling
LL
Chen
Yu-Juan
YJ
Tao
Bei-Bei
BB
Yu
Yong-Chun
YC
Bian
Wei-Hong
WH
Yu
Jing
J
Wang
Yong-Gang
YG
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D000077022:Survivin
C516989:Birc5 protein, rat; D016166:Free Radical Scavengers; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077553:Edaravone; D000983:Antipyrine