Abstract |
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.
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Authors | Xue-Yuan Liu, Ling-Ling Yao, Yu-Juan Chen, Bei-Bei Tao, Yong-Chun Yu, Wei-Hong Bian, Jing Yu, Yong-Gang Wang |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 327
Issue 1-2
Pg. 21-8
(Jul 2009)
ISSN: 1573-4919 [Electronic] Netherlands |
PMID | 19224341
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Birc5 protein, rat
- Free Radical Scavengers
- Microtubule-Associated Proteins
- Survivin
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Edaravone
- Antipyrine
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Topics |
- Animals
- Antipyrine
(analogs & derivatives, pharmacology)
- Apoptosis
- Edaravone
- Free Radical Scavengers
(pharmacology)
- Microtubule-Associated Proteins
(metabolism)
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- PC12 Cells
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats
- Survivin
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