Journal
CELL DEATH AND DIFFERENTIATION
Volume 14, Issue 4, Pages 840-850Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4402071
Keywords
apoptosis; UV-C; Fas ligand; Bcl-x(L); glucocorticoids
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
Ask authors/readers for more resources
Our laboratory has shown that glucocorticoids can inhibit apoptosis in rat hepatoma cells; however, the mechanisms are incompletely understood. To address this issue we sought to determine if glucocorticoid inhibition is effective when death is induced by stimuli that more selectively activate either the intrinsic (UV-C) or extrinsic (FasL) apoptotic pathways. Using flow cytometric analysis, we show that pretreatment of HTC cells with dexamethasone (Dex) inhibits UV-C-but not FasL-induced apoptosis. This inhibition requires Dex pretreatment and can be abrogated by the glucocorticoid antagonist RU486 indicating glucocorticoid receptor-mediated action. Dex increases anti-apoptotic Bcl-x(L) at both mRNA and protein levels. The Bcl-x(L) protein level remains elevated even after apoptosis induction with either UV-C or FasL although only UV-C-induced cell death is inhibited. Repression of Bcl-x(L) protein with siRNA abrogates the anti-apoptotic effect of glucocorticoids. Together these data provide direct evidence that Bcl-x(L) mediates glucocorticoid inhibition of UV-C induced apoptosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available