Apoptosis of CTLL-2 cells induced by an immunosuppressant, ISP-I, is caspase-3 - Like protease - Independent

Toshiyuki Yamaji, Sachiko Nakamura, Hiromu Takematsu, Toshisuke Kawasaki, Yasunori Kozutsumi

研究成果: Article査読

4 被引用数 (Scopus)

抄録

In our previous study, the sphingosine-like immunosuppressant ISP-1 was shown to induce apoptosis in the mouse cytotoxic T cell line CTLL-2. In this study, we characterized the ISP-1 - induced apoptotic pathway. Although caspase-3 -like protease activity increases concomitantly with ISP-1 - induced apoptosis in CTLL-2 cells, the apoptosis is not inhibited by caspase-3 - like protease inhibitors, i.e. DEVD-cho and z-DEVD-fmk. In contrast, sphingosine-induced apoptosis in CTLL-2 cells is caspase-3 - like protease - dependent. A caspase inhibitor with broad specificity, z-VAD-fmk, protects cells from apoptosis induced by ISP-1, indicating that ISP-1 - induced apoptosis is dependent on caspase(s) other than caspase-3. Overexpression of Bcl-2 or Bcl-xL suppresses the apoptosis induced by ISP-1, although sphingosine-induced apoptosis is not efficiently inhibited by Bcl-2. Finally, ISP-1 - induced mitochondrial depolarization, which is thought to be a checkpoint dividing the apoptotic pathway into upstream and downstream stages, is not inhibited by DEVD-cho, but is inhibited by z-VAD-fmk. These data suggest that a pathway dependent on caspase(s) other than caspase-3 is involved upstream of mitochondrial depolarization in ISP-1 - induced apoptosis.

本文言語English
ページ(範囲)521-527
ページ数7
ジャーナルJournal of Biochemistry
129
4
DOI
出版ステータスPublished - 04-2001
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学

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