L-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein
2014 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 12, 23059-23073 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
MDPI , 2014. Vol. 15, no 12, 23059-23073 p.
L-cystathionine; ox-LDL; macrophage; mitochondrial; oxidative stress; apoptosis; caspase-9; caspase-3
IdentifiersURN: urn:nbn:se:liu:diva-113576DOI: 10.3390/ijms151223059ISI: 000346797400089PubMedID: 25514411OAI: oai:DiVA.org:liu-113576DiVA: diva2:783083
Funding Agencies|Major Basic Research Development Program of Peoples Republic of China [2012CB517806, 2013CB933801, 2011CB503904]; National Natural Science Foundation of China [31130030, 81370154, 81121061]; Grant of Ministry of Education, China ; Beijing Natural Science Foundation ; Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education [2014XXGB02]2015-01-232015-01-232016-01-09Bibliographically approved