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  • Glucocorticoids can induce BIM to trigger apoptosis in the absence of BAX and BAK1.

Glucocorticoids can induce BIM to trigger apoptosis in the absence of BAX and BAK1.

Cell death & disease (2020-06-10)
Li Dong, David L Vaux
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Bak antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture
Sigma-Aldrich
Fetal Bovine Serum, Australia origin, suitable for, USDA approved, sterile-filtered, suitable for cell culture, suitable for hybridoma