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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
発行日
2005-12
出版物タイトル
Acta Medica Okayama
59巻
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
English
論文のバージョン
publisher
査読
有り
PubMed ID
Web of Science KeyUT