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L-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein
Peking University, Peoples R China.
Peking University, Peoples R China; Minist Educ, Peoples R China.
Peking University, Peoples R China.
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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
Abstract [en]

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.
Keyword [en]
L-cystathionine; ox-LDL; macrophage; mitochondrial; oxidative stress; apoptosis; caspase-9; caspase-3
National Category
Basic Medicine
URN: urn:nbn:se:liu:diva-113576DOI: 10.3390/ijms151223059ISI: 000346797400089PubMedID: 25514411OAI: 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 [20130001120047]; Beijing Natural Science Foundation [7121014]; Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education [2014XXGB02]

Available from: 2015-01-23 Created: 2015-01-23 Last updated: 2016-01-09Bibliographically approved

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Holmberg, Lukas
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