中国动脉硬化杂志2025，Vol.33Issue(6)：481-492,12.DOI:10.20039/j.cnki.1007-3949.2025.06.004
S1P/S1PR1通过抑制Pyk2减轻H2O2诱导的血管内皮细胞线粒体损伤
S1P/S1PR1 attenuates H2O2-induced mitochondrial damage in vascular endothelial cells by inhibiting Pyk2
摘要
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.关键词
1-磷酸鞘氨醇/富含脯氨酸的酪氨酸激酶2/氧化应激/人脐静脉内皮细胞/线粒体损伤Key words
sphingosine-1-phosphate/proline-rich tyrosine kinase 2/oxidative stress/human umbilical vein endothelial cell/mitochondrial damage分类
医药卫生引用本文复制引用
李朝荃,姚慧,刘婉婷,谢玉鑫,杨皓天,付傲妮,李婧,易光辉..S1P/S1PR1通过抑制Pyk2减轻H2O2诱导的血管内皮细胞线粒体损伤[J].中国动脉硬化杂志,2025,33(6):481-492,12.基金项目
国家自然科学基金项目(81770490) （81770490）
湖南省科技计划项目(2020JJ4535) （2020JJ4535）
