論文 - 詳細
| RRC ID | 42892 |
|---|---|
| 著者 | Murakami Y, Aizu-Yokota E, Sonoda Y, Ohta S, Kasahara T. |
| タイトル | Suppression of endoplasmic reticulum stress-induced caspase activation and cell death by the overexpression of Bcl-xL or Bcl-2. |
| ジャーナル | J Biochem |
| Abstract |
Continuous endoplasmic reticulum (ER) stress, such as the accumulation of unfolded proteins, results in cell death and relates to the pathogenesis of some neurodegenerative diseases. Treatment of brefeldin A, an inhibitor of transport between the ER and Golgi complex, induced cell death during 24 h, which accompanied activation of caspase-2, caspase-3 and caspase-9, starting at 12 h and increasing time-dependently up to 28 h. Caspase-2 was expressed and activated in not only mitochondria and cytosol, but also in the microsomal fraction containing ER and Golgi. Of note is that overexpression of Bcl-x(L) or Bcl-2 in PC12 cells markedly suppressed brefeldin A-induced activation of caspases and resulting cell death. Delivery of anti-Bcl-2 antibody into the Bcl-2-overexpressed cells again recovered apoptosis. While the brefeldin A-treatment induced the phosphorylation of both c-Jun N-terminal kinase (JNK) and p38 MAPK, overexpression of Bcl-x(L) or Bcl-2 reduced the prolonged phosphorylation of JNK, but not of p38 MAPK. Pretreatment with a JNK inhibitor, SP600125, suppressed the brefeldin A-induced caspase-2 activation and cell death significantly. Thus, our results suggest that protective effects of Bcl-x(L) and Bcl-2 against brefeldin A-induced cell death appear to be dependent on the regulation of JNK activation. |
| 巻・号 | 141(3) |
| ページ | 401-10 |
| 公開日 | 2007-3-1 |
| DOI | 10.1093/jb/mvm044 |
| PII | mvm044 |
| PMID | 17301078 |
| MeSH | Animals Anthracenes / pharmacology Apoptosis / drug effects* Brefeldin A / pharmacology Caspase 2 / metabolism* Caspase 9 / metabolism* Cytochromes c / metabolism Endoplasmic Reticulum / drug effects* Endoplasmic Reticulum / enzymology* Enzyme Activation / drug effects Imidazoles / pharmacology JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors NFI Transcription Factors / metabolism* PC12 Cells Proto-Oncogene Proteins c-bcl-2 / biosynthesis* Proto-Oncogene Proteins c-bcl-2 / immunology Pyridines / pharmacology Rats Transfection bcl-X Protein / biosynthesis* |
| IF | 2.476 |
| 引用数 | 35 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |