S1PR2 antagonist protects endothelial cells against high glucose-induced mitochondrial apoptosis through the Akt/GSK-3ß signaling pathway.
Biochem Biophys Res Commun
; 490(3): 1119-1124, 2017 08 26.
Article
en En
| MEDLINE
| ID: mdl-28676392
ABSTRACT
Vascular complications are the main cause of morbidity and mortality associated with type 2 diabetes mellitus. An early hallmark of the onset of vascular complications is endothelial dysfunction and apoptosis. We aimed to explore the role of sphingosine-1-phosphatereceptor 2 (S1PR2) in high glucose-induced endothelial cells apoptosis and to elaborate the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were cultured in a high glucose with or without S1PR2 antagonist. The apoptosis of the cells was measured by flow cytometry and mitochondrial membrane permeability was detected by the fluorescent probe JC-1. The expression of the related protein was determined by western blot. Cell apoptosis and the loss of mitochondrial membrane permeability were induced under high glucose conditions in HUVECs. The expression of mitochondrial apoptosis related protein bax increased and bcl-2 decreased in high glucose-induced HUVECs. The level of cytochrome c released into the cytoplasm increased when cells were exposed to high glucose. In addition, the expression of p-AKT and p-GSK3ß was reduced when HUVECs were treated with high glucose. However, these effects were reversed in HUVECs when cells treated with S1PR2 antagonist. In conclusion, S1PR2 antagonist protects endothelial cells against high glucose-induced mitochondrial apoptosis through the Akt/GSK-3ß signaling pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Piridinas
/
Transducción de Señal
/
Apoptosis
/
Sustancias Protectoras
/
Células Endoteliales
/
Receptores de Lisoesfingolípidos
/
Glucosa
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2017
Tipo del documento:
Article