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

L-cystathionine inhibits the mitochondria-mediated macrophage apoptosis induced by oxidized low density lipoprotein.
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L-胱硫醚抑制氧化低密度脂蛋白诱导的线粒体介导的巨噬细胞凋亡

DOI:
10.3390/ijms151223059
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发表时间:
2014-12-11
影响因子:
5.6
通讯作者:
Jin H
Jin H
中科院分区:
生物学2区
文献类型:
--
作者:
Zhu M;Du J;Chen S;Liu AD;Holmberg L;Chen Y;Zhang C;Tang C;Jin H

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本研究旨在探讨L-胱硫醚对氧化型低密度脂蛋白(ox-LDL)诱导的人巨噬细胞凋亡的调节作用及其可能机制。THP-1细胞经佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)诱导分化为巨噬细胞。在用l-胱硫醚预处理后,将巨噬细胞与ox-LDL孵育。检测超氧阴离子、细胞凋亡、线粒体膜电位和线粒体通透性转换孔(MPTP)开放。测定Caspase-9活性和切割的caspase-3的表达。结果表明,与对照组相比,ox-LDL处理组能显著促进超氧阴离子的产生、细胞色素c(cytc)从线粒体释放到胞浆、caspase-9活性、caspase-3裂解和细胞凋亡,并降低线粒体膜电位和增加MPTP开放。0.3和1.0 mmol/L L L-胱硫醚显著降低ox-LDL + L-胱硫醚巨噬细胞超氧阴离子的产生,增加线粒体膜电位,并显著降低MPTP开放。此外,与ox-LDL处理的细胞相比,l-胱硫醚预处理的细胞中cytc从胞浆中释放到胞质中、caspase-9活性、caspase-3裂解和凋亡水平显著减弱。以上结果提示,L-胱硫醚可通过抑制cytc的释放和caspase的激活,拮抗ox-LDL诱导的巨噬细胞凋亡。
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.
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发表时间: 2000-03-16
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