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.

Details

Title
Glucocorticoids can induce BIM to trigger apoptosis in the absence of BAX and BAK1
Author
Li, Dong 1 ; Vaux, David L 2 

 1G Royal Parade, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The University of Melbourne, Department of Medical Biology, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
 1G Royal Parade, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia (GRID:grid.1008.9); The University of Melbourne, Department of Medical Biology, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
Publication year
2020
Publication date
Jun 2020
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2410666417
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.