S1P/S1PR1 attenuates H2O2-induced mitochondrial damage in vascular endothelial cells by inhibiting Pyk2
10.20039/j.cnki.1007-3949.2025.06.004
- VernacularTitle:S1P/S1PR1通过抑制Pyk2减轻H2O2诱导的血管内皮细胞线粒体损伤
- Author:
Chaoquan LI
1
;
Hui YAO
;
Wanting LIU
;
Yuxin XIE
;
Haotian YANG
;
Aoni FU
;
Jing LI
;
Guanghui YI
Author Information
1. 南华大学基础医学院心血管疾病研究所
- Publication Type:Journal Article
- Keywords:
sphingosine-1-phosphate;
proline-rich tyrosine kinase 2;
oxidative stress;
human umbilical vein endothelial cell;
mitochondrial damage
- From:
Chinese Journal of Arteriosclerosis
2025;33(6):481-492
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.
