論文 - 詳細
| RRC ID | 43002 |
|---|---|
| 著者 | Seyfried J, Wüllner U. |
| タイトル | Inhibition of thioredoxin reductase induces apoptosis in neuronal cell lines: role of glutathione and the MKK4/JNK pathway. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
The Thioredoxin (Trx)/Thioredoxin reductase (TrxR)-system has emerged as a crucial component of many cellular functions particularly antioxidant defence. We investigated the effect of the selective TrxR inhibitor 1-chloro-2,4-dinitrobenzene (CDNB) on survival and redox status in neuronal cell lines. CDNB was found to cause apoptosis without depletion of glutathione or loss of mitochondrial complex I-activity. Cells treated with CDNB displayed an early increase of reactive oxygen species and rapid activation of stress inducible protein kinases c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase kinase 4 (MKK4). Thus TrxR inhibition by CDNB results in generation of reactive oxygen species and subsequent activation of stress-inducible kinases without impairment of the cellular antioxidant status or mitochondrial function. Inhibition of the specific kinases involved in cell death triggered by Trx/TrxR dysfunction could represent a novel and selective therapeutic approach in neurodegenerative disorders. |
| 巻・号 | 359(3) |
| ページ | 759-64 |
| 公開日 | 2007-8-3 |
| DOI | 10.1016/j.bbrc.2007.05.176 |
| PII | S0006-291X(07)01170-9 |
| PMID | 17559804 |
| MeSH | Animals Apoptosis / drug effects* Cell Line Dinitrochlorobenzene / toxicity Enzyme Inhibitors / pharmacology Ethacrynic Acid / toxicity Glutathione / metabolism* JNK Mitogen-Activated Protein Kinases / metabolism* MAP Kinase Kinase 4 / metabolism* MAP Kinase Signaling System / drug effects* Microscopy, Electron Neurons / cytology Neurons / drug effects Neurons / metabolism* PC12 Cells Rats Reactive Oxygen Species / metabolism Thioredoxin-Disulfide Reductase / antagonists & inhibitors* Thioredoxin-Disulfide Reductase / metabolism |
| IF | 2.985 |
| 引用数 | 26 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |