CD4 super(+)CD8 super(+) thymocytes are induced to cell death by a small dose of puromycin via ER stress

• Published in: Cellular immunology 2009-01, Vol.260 (1), p.21-27
• Main Authors: Oguma, T, Ono, T, Kajiwara, T, Sato, M, Miyahira, Y, Arino, H, Yoshihara, Y, Tadakuma, T
• Format: Article
• Language: English
• ISSN: 0008-8749
• DOI: 10.1016/j.cellimm.2009.07.002

When the CD4 super(+)CD8 super(+) thymic lymphoma cells were treated with puromycin, we found that most of the cells died at 0.3-1 mu g/ml of puromycin within 24h. However, cell death was greatly reduced when the dose of puromycin was increased. Similar dose-pattern of cell death was observed in thymocytes and the sensitivity to puromycin was greater in CD4 super(+)CD8 super(+) thymocytes than CD4 super(+)CD8 super(-) thymocytes. The induction of apoptosis was blocked by the protein synthesis inhibitor cycloheximide, and to some extent by transfection of Bcl-xL or Bcl-2 genes. Expression of GRP78 was up-regulated after treatment with a small dose of puromycin, and the cell death by puromycin was blocked in the presence of caspase 12 inhibitor. These results indicated that the induction of cell death by low-dose puromycin was due to endoplasmic reticulum stress. Furthermore, we found that dexamethasone, a synthetic glucocorticoid, and puromycin worked synergistically to induce cell death in thymocytes.