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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kagami, Shoji Fujita, Yoshiko Ishizawa, Keisuke Tamaki, Toshiaki Kirima, Kazuyoshi Tsuchiya, Koichiro Kyaw, Moe Kogame, Toshiaki Yoshizumi, Masanori Suzaki, Yuki |
| Description | Author Affiliation: Yoshizumi M ( Department of Pharmacology, The University of Tokushima School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. yoshizu@basic.med.tokushima-u.ac.jp) |
| Abstract | 1: Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) is a selenoorganic compound exhibiting both glutathione peroxidase activity and antioxidant activity. Although it has been reported that ebselen is effective for oxidative stress-induced neuronal damage both in vivo and clinically, the precise mechanisms of the efficacy have not yet been elucidated. Thus, we hypothesized that ebselen may affect reactive oxygen species-induced mitogen-activated protein (MAP) kinase activation in cultured PC12 cells. 2: Our findings showed that hydrogen peroxide (H(2)O(2)) stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 in PC12 cells, which is a model of catecholamine-containing neurons. 3: H(2)O(2)-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 activation by H(2)O(2) were not affected by ebselen. 4: Inhibition by ebselen of H(2)O(2)-induced hydroxyl radical generation in PC12 cells was observed using electron paramagnetic resonance measurements. Ebselen also inhibited H(2)O(2)-induced increases in DNA binding activity of activator protein-1 (AP-1), a downstream transcription factor of JNK, composed of the c-Jun homo/heterodimer. 5: Finally, pretreatment of cells with ebselen resulted in a significant recovery from cell death including apoptosis by H(2)O(2) in PC12 cells. 6 These findings suggest that ebselen attenuates oxidative stress-induced neuronal cell death through the inhibition of the JNK and AP-1 signalling pathway. Thus, inhibition of JNK by ebselen may imply its usefulness for treatment of ischaemic cerebral diseases relevant to neuronal cell death. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 136 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2002-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Antioxidants Pharmacology Apoptosis Drug Effects Azoles Mitogen-Activated Protein Kinases Antagonists & Inhibitors Organoselenium Compounds Oxidative Stress Transcription Factor AP-1 Physiology Analysis Of Variance Animals Cell Survival DNA Fragmentation Electron Spin Resonance Spectroscopy Enzyme Activation Hydrogen Peroxide JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1 Metabolism Mitogen-Activated Protein Kinase 3 PC12 Cells Reactive Oxygen Species Signal Transduction Time Factors P38 Mitogen-Activated Protein Kinases Comparative Study |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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