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L-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein
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- Zhu, Mingzhu (author)
- Peking University, Peoples R China
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- Du, Junbao (author)
- Peking University, Peoples R China; Minist Educ, Peoples R China
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- Chen, Siyao (author)
- Peking University, Peoples R China
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- Dong Liu, Angie (author)
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- (creator_code:org_t)
- 2014-12-11
- 2014
- English.
- In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 15:12, s. 23059-23073
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- L-cystathionine; ox-LDL; macrophage; mitochondrial; oxidative stress; apoptosis; caspase-9; caspase-3
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- ref (subject category)
- art (subject category)
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- Zhu, Mingzhu
- Du, Junbao
- Chen, Siyao
- Dong Liu, Angie
- Holmberg, Lukas
- Chen, Yonghong
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- Zhang, Chunyu
- Tang, Chaoshu
- Jin, Hongfang
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- Linköping University
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