Differential involvement of p38 MAP kinase pathway and Bax translocation in the mitochondria-mediated cell death in TCR- and dexamethasone-stimulated thymocytes

✍ Scribed by Tomoyasu Yoshino; Hiroyuki Kishi; Takuya Nagata; Kazuhiro Tsukada; Shigeru Saito; Atsushi Muraguchi

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 123 KB
• Volume: 31
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200109)31:9<2702::aid-immu2702>3.0.co;2-8

✦ Synopsis

Mitochondria play a central role in many apoptotic reactions. Although mitochondrial apoptotic changes and caspase activation have been demonstrated in the apoptotic thymocytes, cell death signal through mitochondria in TCR-stimulated thymocytes has not been fully understood. In this study, we show that TCR stimulation induced disruption of mitochondrial transmembrane potential ( ¿ $ m ), the cytochrome c release from mitochondira, capase-3 activation, and the cell death of thymocytes. Bongkrekic acid, an inhibitor of ¿ $ m disruption, blocked the cytochrome c release from mitochondria and the following caspase-3mediated cell death. Furthermore, a pro-apoptotic Bcl-2 family protein, Bax, but not Bad or Bid, was translocated from cytosol to mitochondria in TCR-stimulated thymocytes. This translocation and the following apoptotic changes were inhibited by SB203580, a p38 kinase inhibitor, in a specific manner. These results suggest that activated p38 kinase pathway by TCR stimulation induces translocation of Bax to mitochondria, causing ¿ $ m disruption, and the release of cytochrome c, which finally induces caspase-3-mediated apoptosis in thymocytes.