ID | 31959 |
JaLCDOI | |
フルテキストURL | |
著者 |
Huang, Jian
Shenyang Pharmaceutical University
Wu, Lijun
Shenyang Pharmaceutical University
Tashiro, Shin-ichi
Showa Pharmaceutical University
Onodera, Satoshi
Showa Pharmaceutical University
Ikejima, Takashi
Shenyang Pharmaceutical University
|
抄録 | We investigated the mechanism of the pan-caspase inhibitor z-VAD-fmk's augmentation of TNFalpha-induced L929 cell death and found this mechanism differs from that of TNFalpha-induced L929 cell death. In the presence of 20 ng/ml TNFalpha, z-VAD-fmk initiated apoptosis and necrosis in the majority of L929 cells as measured by an agarose gel electrophoresis and lactate dehydrogenase(LDH)activity based assay. Mitochondrial permeability transition (MPT) inhibitor (cyclosporine A) effectively inhibited z-VAD-fmk-augmented cell death. In addition, z-VAD-fmk plus TNFalpha increased Bax expression without affecting Bcl-2 and cytochrome expression. Western-blot analysis showed that z-VAD-fmk plus TNFalpha caused persistent JNK activation and ERK inactivation. Poly(ADP-ribose) polymerase (PARP) inhibitor (DPQ) effectively reversed the cell death which was augmented by z-VAD-fmk, and z-VAD-fmk plus TNFalpha also caused PARP cleavage to an 85 KDa fragment. These results indicate that in the presence of TNFalpha, z-VAD-fmk further augments cell death which requires the mitochondrial permeability transition and the JNK activation. However, we did not detect the changes in cytochrome c expression and the participation of caspase-9 in this process, suggesting that there might exist an unknown signal pathway(s) from the mitochondria to the downstream protein PARP, which is cleaved in a caspase-independent manner. |
キーワード | TNF?
caspase
Bax/Bcl-2
MAPK
PARP
|
Amo Type | Original Article
|
出版物タイトル |
Acta Medica Okayama
|
発行日 | 2005-12
|
巻 | 59巻
|
号 | 6号
|
出版者 | Okayama University Medical School
|
開始ページ | 253
|
終了ページ | 260
|
ISSN | 0386-300X
|
NCID | AA00508441
|
資料タイプ |
学術雑誌論文
|
言語 |
英語
|
論文のバージョン | publisher
|
査読 |
有り
|
PubMed ID | |
Web of Science KeyUT |