载脂蛋白E
电压依赖性阴离子通道
线粒体
VDAC1型
脂蛋白
细胞生物学
载脂蛋白B
生物
体内
线粒体分裂
化学
内科学
内分泌学
生物化学
胆固醇
医学
基因
细菌外膜
生物技术
大肠杆菌
疾病
作者
Wei-Yu Chen,Yunfang Chen,Hua-Cheng Chan,Ching‐Hu Chung,Hsien Yu Peng,Yu-Cheng Ho,Chu‐Huang Chen,Kuan‐Cheng Chang,Chih-Hsin Tang,An‐Sheng Lee
标识
DOI:10.1016/j.metabol.2020.154227
摘要
Objective L5, a highly electronegative subtype of low-density lipoprotein (LDL), is likely associated with the development of atherosclerosis and cardiovascular diseases. Normal LDL is composed mainly of apolipoprotein (Apo) B, but L5 has additional proteins such as ApoE. We previously demonstrated that L5 induces endothelial cell senescence by increasing mitochondrial reactive oxygen species. In the present study, we examined the effect of L5 on mitochondrial function in cardiomyocytes. Methods We used the Seahorse XF24 extracellular flux analyzer to examine the effect of L5 and its components on mitochondrial energy production. The effects of L5 on mitochondrial morphology were examined by immunofluorescence using MitoTracker Green FM and the corresponding probes in H9c2 cardiomyoblasts. Mitochondrial permeability was assessed by using a calcium-induced swelling assay with a voltage-dependent anion-selective channel (VDAC) inhibitor to determine VDAC-dependence both in vitro and in vivo. L5 without ApoE, referred to as △L5, was used to clarify the role of ApoE in L5-induced mitochondrial dysfunction. Results L5 not only significantly decreased basal (P < 0.05) and maximal respiration (P < 0.01) but also reduced spare respiratory capacity (P < 0.01) in H9c2 cells. Additionally, L5 caused phosphorylation of Drp1 and mitochondrial fission. Recombinant ApoE mimicked the mitochondrial effects of L5, but △L5 did not cause similar effects. After entering cells, ApoE on L5 colocalized with mitochondrial VDAC and caused mitochondria swelling both in vitro and in vivo. This effect was also seen with recombinant ApoE but not △L5. Conclusions ApoE may play an important role in electronegative LDL-induced mitochondrial dysfunction through the opening of the mitochondrial permeability transition pore via the interaction of ApoE and VDAC.
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