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

International Journal of Molecular Sciences

Mingzhu Zhu¹  Junbao Du¹  Siyao Chen¹  Angie Dong Liu²  Lukas Holmberg²  Yonghong Chen¹  Chunyu Zhang¹  Chaoshu Tang³  Hongfang Jin¹ 

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

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

DOI  :  10.3390/ijms151223059

来源: mdpi

【 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) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after 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 results showed 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 in ox-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 and caspase activation.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.