Cytotoxicity of lipid-free apolipoprotein B
Cytotoxicity of lipid-free apolipoprotein B
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DOI：
10.1016/j.bbamem.2008.08.012
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Handa, Tetsurou
中科院分区：
文献类型：
--
作者：
Morita, Shin-ya;Deharu, Yuko;Handa, Tetsurou
为了研究载脂蛋白B（apo B）对细胞活力的影响，我们使用无脂质的apo B作为变性apo B的模型。无脂载脂蛋白B对J774巨噬细胞、CHO细胞和HepG 2细胞具有细胞毒性，而与低密度脂蛋白（LDL）结合的载脂蛋白A-I对细胞活力无影响。通过caspase-3激活和膜联蛋白V结合评估无脂质apoB诱导J774巨噬细胞凋亡。LDL受体、硫酸乙酰肝素蛋白聚糖和A类清道夫受体参与了无脂载脂蛋白B的结合/摄取，但细胞对无脂载脂蛋白B的结合/摄取与细胞毒性无关。无脂载脂蛋白B破坏含有钙黄绿素的大单层囊泡的脂质双层。我们评估apoB和细胞膜之间的相互作用，通过监测细胞内Ca 2+浓度的变化，使用Fura-2。并发现无脂质的apoB在不存在或存在由受体介导的细胞结合/摄取的抑制剂的情况下迅速破坏细胞膜。因此，它表明，脂质无载脂蛋白B诱导细胞死亡的质膜的干扰。除了修饰LDL中的其他脂质成分外，apoB本身具有诱导细胞凋亡的能力，并且在动脉粥样硬化病变的发展中起着至关重要的作用。(C)2008 Elsevier B. V.保留所有权利。
To investigate the effect of apolipoprotein B (apoB) on cell viability, we used lipid-free apoB as a model for denatured apoB. Lipid-free apoB had cytotoxicity to J774 macrophages, CHO cells and HepG2 cells, whereas apoB bound to low density lipoprotein (LDL) and lipid-free apolipoprotein A-I had no effect on cell viability. Lipid-free apoB induced apoptosis in J774 macrophages assessed by caspase-3 activation and annexin V binding. LDL receptor, heparan sulfate proteoglycans, and class A scavenger receptor were involved in the binding/uptake of lipid-free apoB, but lipid-free apoB binding/uptake by the cells did not correlate with cytotoxicity. Lipid-free apoB disrupted the lipid bilayer of large unilamellar vesicles containing calcein. We evaluated the interaction between apoB and cellular membrane by monitoring the change in intracellular Ca2+ concentration using Fura-2. and found that lipid-free apoB rapidly disrupted the cellular membrane in the absence or presence of the inhibitors for cellular binding/uptake mediated by the receptors. Therefore, it is suggested that lipid-free apoB induces cell death by disturbance of the plasma membrane. In addition to other lipid component in modified LDL, apoB itself has an ability to induce apoptosis and plays a crucial role in the development of atherosclerotic lesions. (C) 2008 Elsevier B.V. All rights reserved.