Dexamethasone sensitizes to ferroptosis by glucocorticoid receptor-induced dipeptidase-1 expression and glutathione depletion.
Carbolines
/ adverse effects
Cell Line
Dexamethasone
/ pharmacology
Dipeptidases
/ genetics
Ferroptosis
/ drug effects
Fluorescent Antibody Technique
GPI-Linked Proteins
/ genetics
Gene Expression Regulation
/ drug effects
Gene Knockdown Techniques
Glutathione
/ metabolism
Humans
Immunophenotyping
Oxidation-Reduction
/ drug effects
Piperazines
/ adverse effects
Receptors, Glucocorticoid
/ metabolism
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
04 02 2022
04 02 2022
Historique:
entrez:
2
2
2022
pubmed:
3
2
2022
medline:
9
2
2022
Statut:
ppublish
Résumé
Dexamethasone is widely used as an immunosuppressive therapy and recently as COVID-19 treatment. Here, we demonstrate that dexamethasone sensitizes to ferroptosis, a form of iron-catalyzed necrosis, previously suggested to contribute to diseases such as acute kidney injury, myocardial infarction, and stroke, all of which are triggered by glutathione (GSH) depletion. GSH levels were significantly decreased by dexamethasone. Mechanistically, we identified that dexamethasone up-regulated the GSH metabolism regulating protein dipeptidase-1 (DPEP1) in a glucocorticoid receptor (GR)-dependent manner. DPEP1 knockdown reversed the phenotype of dexamethasone-induced ferroptosis sensitization. Ferroptosis inhibitors, the DPEP1 inhibitor cilastatin, or genetic
Identifiants
pubmed: 35108055
doi: 10.1126/sciadv.abl8920
pmc: PMC8809683
doi:
Substances chimiques
Carbolines
0
GPI-Linked Proteins
0
Piperazines
0
RSL3 compound
0
Receptors, Glucocorticoid
0
erastin
0
Dexamethasone
7S5I7G3JQL
Dipeptidases
EC 3.4.13.-
dipeptidase 1
EC 3.4.13.19
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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