Empagliflozin reduces endoplasmic reticulum stress associated TXNIP/NLRP3 activation in tunicamycin-stimulated aortic endothelial cells.
Naunyn Schmiedebergs Arch Pharmacol
; 397(1): 267-279, 2024 01.
Article
en En
| MEDLINE
| ID: mdl-37421429
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have proven to be of therapeutic significance for cardiovascular diseases beyond the treatment of type 2 diabetes. Recent studies have demonstrated the beneficial effects of SGLT2i on endothelial cell (EC) dysfunction, but the underlying cellular mechanisms remain to be clarified. In this study, we sought to understand the effect of empagliflozin (EMPA; Jardiance®) on cell homeostasis and endoplasmic reticulum (ER) stress signaling. ER stress was induced by tunicamycin (Tm) in human abdominal aortic ECs treated with EMPA over 24 h. Tm-induced ER stress caused increases in the protein expression of thioredoxin interacting protein (TXNIP), NLR-family pyrin domain-containing protein 3 (NLRP3), C/EBP homologous protein (CHOP), and in the ratio of phospho-eIF2α/eIF2α. EMPA (50-100 µM) resulted in a dampened downstream activation of ER stress as seen by the reduced expression of CHOP and TXNIP/NLRP3 in a dose-dependent manner. Nuclear factor erythroid 2-related factor 2 (nrf2) translocation was also attenuated in EMPA-treated ECs. These results suggest that EMPA improves redox signaling under ER stress which in turn attenuates the activation of TXNIP/NLRP3.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Proteína con Dominio Pirina 3 de la Familia NLR
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Naunyn Schmiedebergs Arch Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Alemania