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Int. J. Mol. Sci. 2014, 15(12), 23059-23073; doi:10.3390/ijms151223059

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

1
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
2
Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China
3
Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden
4
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China
*
Author to whom correspondence should be addressed.
Received: 27 October 2014 / Revised: 28 November 2014 / Accepted: 4 December 2014 / Published: 11 December 2014
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Abstract

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. View Full-Text
Keywords: l-cystathionine; ox-LDL; macrophage; mitochondrial; oxidative stress; apoptosis; caspase-9; caspase-3 l-cystathionine; ox-LDL; macrophage; mitochondrial; oxidative stress; apoptosis; caspase-9; caspase-3
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhu, M.; Du, J.; Chen, S.; Liu, A.D.; Holmberg, L.; Chen, Y.; Zhang, C.; Tang, C.; Jin, H. l-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein. Int. J. Mol. Sci. 2014, 15, 23059-23073.

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