L-cystathionine inhibits the mitochondria-mediated macrophage apoptosis induced by oxidized low density lipoprotein

• Published in: International journal of molecular sciences 2014-12, Vol.15 (12), p.23059-23073
• Main Authors: Zhu, Mingzhu, Du, Junbao, Chen, Siyao, Liu, Angie Dong, Holmberg, Lukas, Chen, Yonghong, Zhang, Chunyu, Tang, Chaoshu, Jin, Hongfang
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Caspase 9 - metabolism; caspase-3; caspase-9; Cell Line; Cellular biology; Cystathionine - pharmacology; Cytochromes c - metabolism; Enzymes; Humans; l-cystathionine; Lipoproteins, LDL - pharmacology; Low density lipoprotein; macrophage; Macrophages - drug effects; Macrophages - metabolism; Membrane Potential, Mitochondrial; Mitochondria - metabolism; mitochondrial; ox-LDL; Oxidative stress; Superoxides - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms151223059

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.