Glucocorticoids can induce BIM to trigger apoptosis in the absence of BAX and BAK1
- Details
- Publication Year 2020-06-08,Volume 11,Issue #6,Page 442
- Journal Title
- Cell Death & Disease
- Publication Type
- Journal Article
- Abstract
- Cells from two murine lymphoid lines died 24-48 h after treatment with the glucocorticoid dexamethasone. Deletion of Bax and Bak1 prevented rapid apoptosis, but treatment with dexamethasone for greater 6 days still led to cell death that was characterized by release of cytochrome c into the cytosol, activation of caspases, and loss of cell membrane integrity. In WEHI7 thymoma cells, this did not occur when Bcl2l11 (Bim) was deleted in addition to Bax and Bak1. When these triple mutant lines were exposed to dexamethasone for 10 days, they arrested, but after dexamethasone was removed, they had 10-fold higher clone forming efficiency than Bax/Bak1 double knock-out cells. Although induced over-expression of BIMs alone was not sufficient to induce the death of Bax(-/-)Bak1(-/-)Bim(-/-) cells, they did die when BIMs was induced in the presence of dexamethasone. These results suggest that dexamethasone induces production of BIM together with other, as yet unidentified proteins, that cause release of cytochrome c and apoptosis in the absence of BAX and BAK1.
- Publisher
- NPG
- Research Division(s)
- Inflammation
- PubMed ID
- 32513923
- Publisher's Version
- https://doi.org/10.1038/s41419-020-2599-5
- Open Access at Publisher's Site
https://doi.org/10.1038/s41419-020-2599-5- NHMRC Grants
- NHMRC/1113133, NHMRC/1135864,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-06-15 10:33:56
Last Modified: 2020-06-15 10:37:01