Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets

被引:10
|
作者
Sazaki, Iku [1 ]
Sakurai, Toshihiro [1 ]
Yamahata, Arisa [1 ]
Mogi, Sumire [1 ]
Inoue, Nao [1 ]
Ishida, Koutaro [1 ]
Kikkai, Ami [1 ]
Takeshita, Hana [1 ]
Sakurai, Akiko [1 ]
Takahashi, Yuji [2 ]
Chiba, Hitoshi [3 ]
Hui, Shu-Ping [1 ]
机构
[1] Hokkaido Univ, Fac Hlth Sci, Sapporo 0600812, Japan
[2] Hlth Sci Univ Hokkaido, Sch Med Technol, Sapporo 0028072, Japan
[3] Sapporo Univ Hlth Sci, Dept Nutr, Sapporo 0070894, Japan
基金
日本学术振兴会;
关键词
LDL; non-alcoholic steatohepatitis; non-alcoholic fatty liver disease; liquid chromatography-mass spectrometry; lipidomics; FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; DIET; ACCUMULATION; EXPRESSION; PRODUCTS; LDL;
D O I
10.3390/ijms24054281
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidized low-density lipoproteins (oxLDLs) induce oxidative stress in the liver tissue, leading to hepatic steatosis, inflammation, and fibrosis. Precise information on the role of oxLDL in this process is needed to establish strategies for the prevention and management of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Here, we report the effects of native LDL (nLDL) and oxLDL on lipid metabolism, lipid droplet formation, and gene expression in a human liver-derived C3A cell line. The results showed that nLDL induced lipid droplets enriched with cholesteryl ester (CE) and promoted triglyceride hydrolysis and inhibited oxidative degeneration of CE in association with the altered expression of LIPE, FASN, SCD1, ATGL, and CAT genes. In contrast, oxLDL showed a striking increase in lipid droplets enriched with CE hydroperoxides (CE-OOH) in association with the altered expression of SREBP1, FASN, and DGAT1. Phosphatidylcholine (PC)-OOH/PC was increased in oxLDL-supplemented cells as compared with other groups, suggesting that oxidative stress increased hepatocellular damage. Thus, intracellular lipid droplets enriched with CE-OOH appear to play a crucial role in NAFLD and NASH, triggered by oxLDL. We propose oxLDL as a novel therapeutic target and candidate biomarker for NAFLD and NASH.
引用
收藏
页数:15
相关论文
共 30 条
  • [21] Astragaloside IV Protects Against Oxidized Low-Density Lipoprotein (ox-LDL)-Induced Endothelial Cell Injury by Reducing Oxidative Stress and Inflammation
    Zhu, Zhongsheng
    Li, Jinyu
    Zhang, Xiaorong
    MEDICAL SCIENCE MONITOR, 2019, 25 : 2132 - 2140
  • [22] Downregulation of microRNA-34a inhibits oxidized low-density lipoprotein-induced apoptosis and oxidative stress in human umbilical vein endothelial cells
    Zhong, Xiaoming
    Li, Peng
    Li, Juan
    He, Ruili
    Cheng, Guanchang
    Li, Yanming
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2018, 42 (02) : 1134 - 1144
  • [23] PTPRO Promotes Oxidized Low-Density Lipoprotein Induced Oxidative Stress and Cell Apoptosis through Toll-Like Receptor 4/Nuclear Factor kB Pathway
    Liang, Caihong
    Wang, Xiaochen
    Hu, Jianping
    Lian, Xiaoqing
    Zhu, Tiantian
    Zhang, Hui
    Gu, Ning
    Li, Jun
    CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2017, 42 (02) : 495 - 505
  • [24] Curcumin pretreatment protects against PM2.5-induced oxidized low-density lipoprotein-mediated oxidative stress and inflammation in human microvascular endothelial cells
    Shi, Jun
    Deng, Huiping
    Zhang, Min
    MOLECULAR MEDICINE REPORTS, 2017, 16 (03) : 2588 - 2594
  • [25] Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells
    Hao, Shuangying
    Ji, Jiajie
    Zhao, Hongting
    Shang, Longcheng
    Wu, Jing
    Li, Huihui
    Qiao, Tong
    Li, Kuanyu
    MOLECULES, 2015, 20 (12): : 21287 - 21297
  • [27] MiR-140-5p inhibits oxidized low-density lipoprotein-induced oxidative stress and cell apoptosis via targeting toll-like receptor 4
    Liu, Huifang
    Mao, Ziming
    Zhu, Jing
    Shen, Minyan
    Chen, Fengling
    GENE THERAPY, 2021, 28 (7-8) : 413 - 421
  • [28] Chemical Recognition of Oxidation-Specific Epitopes in Low-Density Lipoproteins by a Nanoparticle Based Concept for Trapping, Enrichment, and Liquid Chromatography-Tandem Mass Spectrometry Analysis of Oxidative Stress Biomarkers
    Haller, Elisabeth
    Stuebiger, Gerald
    Lafitte, Daniel
    Lindner, Wolfgang
    Laemmerhofer, Michael
    ANALYTICAL CHEMISTRY, 2014, 86 (19) : 9954 - 9961
  • [29] Protein disulfide-isomerase A3 knockdown attenuates oxidized low-density lipoprotein-induced oxidative stress, inflammation and endothelial dysfunction in human umbilical vein endothelial cells by downregulating activating transcription factor 2
    Jia, Jing
    Wang, Yueping
    Huang, Ruijuan
    Du, Fengxia
    Shen, Xiaozhu
    Yang, Qiurong
    Li, Juan
    BIOENGINEERED, 2022, 13 (01) : 1436 - 1446
  • [30] Miltirone protects human EA.hy926 endothelial cells from oxidized low-density lipoprotein-derived oxidative stress via a heme oxygenase-1 and MAPK/Nrf2 dependent pathway
    Zhang, Liu
    Zhang, Hui
    Li, Xueyan
    Jia, Bingjie
    Yang, Yuyu
    Zhou, Ping
    Li, Ping
    Chen, Jun
    PHYTOMEDICINE, 2016, 23 (14) : 1806 - 1813