l-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized LowDensity Lipoprotein

International Journal of Molecular Sciences

Lukas Holmberg¹  Angie Dong Liu¹  Junbao Du²  Mingzhu Zhu²  Chunyu Zhang²  Siyao Chen²  Yonghong Chen²  Hongfang Jin²  Chaoshu Tang³ 

[1] Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden;Department of Pediatrics, Peking University First Hospital, Beijing 100034, China;Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China;

关键词: l-cystathionine;    ox-LDL;    macrophage;    mitochondrial;    oxidative stress;    apoptosis;    caspase-9;    caspase-3;   

DOI  :  10.3390/ijms151223059

来源: DOAJ

【 摘 要 】

This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) andits possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDLafter pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The resultsshowed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening inox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release andcaspase activation.

【 授权许可】

Unknown