Title :

Macromolecular synthesis inhibitors perturb glucocorticoid receptor trafficking

Author(s) :

Dezitter, Xavier [Auteur]
Masselot, Bernadette [Auteur]
Tardivel, Meryem [Auteur]
Mereau-Richard, Claude [Auteur]
Formstecher, Pierre [Auteur]
Idziorek, Thierry [Auteur]

Journal title :

The Journal of steroid biochemistry and molecular biology

Abbreviated title :

J. Steroid Biochem. Mol. Biol.

Volume number :

126

Pages :

104-112

Publication date :

2011-09-01

ISSN :

0960-0760

English keyword(s) :

Inhibitors
Thymocytes
Apoptosis
Glucocorticoids
Translation
Transcription
Cycloheximide
Actinomycin D

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

The ability of inhibitors of transcription and translation to prevent glucocorticoid-induced apoptosis has been interpreted to indicate that the cell death machinery requires de novo protein synthesis. The transcriptional ...
Show more >The ability of inhibitors of transcription and translation to prevent glucocorticoid-induced apoptosis has been interpreted to indicate that the cell death machinery requires de novo protein synthesis. The transcriptional inhibitors actinomycin D (Act D) and DRB as well as the translational inhibitors CHX and puromycin inhibited early loss of mitochondrial membrane integrity in a dose-dependent manner. This effect was not observed with the transcriptional inhibitor α-amanitin suggesting they may have additional effects. Their role in the glucocorticoid receptor (GR) intracellular trafficking was therefore investigated. Here, we show that Act D and CHX reduced glucocorticoid binding, GR turnover and impaired GR nuclear translocation. We performed the same experiments in different thymocyte subpopulations of Balb/c mice. At the highest dose tested, actinomycin D and cycloheximide abolished glucocorticoid-induced cell death of CD4+CD8+ and CD4+CD8-. In all subsets, Act D, DRB, as well as CHX and puromycin prevented receptor nuclear translocation, indicating a general alteration of GR trafficking. Overall, our data support a direct effect of macromolecular inhibitors on GR activation and trafficking. Finally, direct alterations of the functional properties of the glucocorticoid receptor might be responsible for cell death prevention by actinomycin D, DRB, cycloheximide and puromycin.Show less >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:08:46Z