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 50 条
  • [41] Oxidized low-density lipoprotein increases osteopontin expression by generation of oxidative stress
    Maziere, Cecile
    Gomila, Cathy
    Maziere, Jean-Claude
    FREE RADICAL BIOLOGY AND MEDICINE, 2010, 48 (10) : 1382 - 1387
  • [42] ATM protects against oxidative stress induced by oxidized low-density lipoprotein
    Semlitsch, Michaela
    Shackelford, Rodney E.
    Zirkl, Sandra
    Sattler, Wolfgang
    Malle, Ernst
    DNA REPAIR, 2011, 10 (08) : 848 - 860
  • [43] OXIDIZED LOW-DENSITY LIPOPROTEINS (OXLDL) PLASMA LEVELS AND OXLDL TO LDL RATIO - ARE THEY REAL OXIDATIVE STRESS MARKERS IN DIALYSED PATIENTS?
    Pawlak, D.
    Mysliwiec, M.
    Pawlak, K.
    ATHEROSCLEROSIS, 2014, 235 (02) : E164 - E165
  • [44] Glutathione and Oxidized Low-Density Lipoprotein as Biomarkers of Oxidative Stress in Essential Hypertension
    Sahito, Falak Sehar
    Imtiaz, Fauzia
    Qamar, Ambreen
    Bhatty, Shaheen
    Waseem, Hira Fatima
    JOURNAL OF THE LIAQUAT UNIVERSITY OF MEDICAL AND HEALTH SCIENCES, 2023, 22 (03): : 201 - 205
  • [45] VERY LOW-DENSITY LIPOPROTEINS STIMULATE CHOLESTERYL ESTER FORMATION IN U937 MACROPHAGES - HETEROGENEITY AND BIOLOGIC VARIATION AMONG NORMAL HUMANS
    SACKS, FM
    BRESLOW, JL
    ARTERIOSCLEROSIS, 1987, 7 (01): : 35 - 46
  • [46] Oxidized Low-Density Lipoprotein-Dependent Platelet-Derived Microvesicles Trigger Procoagulant Effects and Amplify Oxidative Stress
    Wang, Hua
    Wang, Zhi-Hao
    Kong, Jing
    Yang, Meng-Yun
    Jiang, Gui-Hua
    Wang, Xu-Ping
    Zhong, Ming
    Zhang, Yun
    Deng, Jing-Ti
    Zhang, Wei
    MOLECULAR MEDICINE, 2012, 18 (02) : 159 - 166
  • [47] Oxidized Low-Density Lipoprotein-Dependent Platelet-Derived Microvesicles Trigger Procoagulant Effects and Amplify Oxidative Stress
    Hua Wang
    Zhi-Hao Wang
    Jing Kong
    Meng-Yun Yang
    Gui-Hua Jiang
    Xu-Ping Wang
    Ming Zhong
    Yun Zhang
    Jing-Ti Deng
    Wei Zhang
    Molecular Medicine, 2012, 18 : 159 - 166
  • [48] Nonphysiological overexpression of low-density lipoprotein receptors causes pathological intracellular lipid accumulation and the formation of cholesterol and cholesteryl ester crystals in vitro
    Heeren, J
    Steinwaerder, DS
    Schnieders, F
    Cichon, G
    Strauss, M
    Beisiegel, U
    JOURNAL OF MOLECULAR MEDICINE-JMM, 1999, 77 (10): : 735 - 743
  • [49] Nonphysiological overexpression of low-density lipoprotein receptors causes pathological intracellular lipid accumulation and the formation of cholesterol and cholesteryl ester crystals in vitro
    Jörg Heeren
    Dirk S. Steinwaerder
    Frank Schnieders
    Günther Cichon
    Michael Strauss
    Ulrike Beisiegel
    Journal of Molecular Medicine, 1999, 77 : 735 - 743
  • [50] CHOLESTERYL ESTER-RICH MICRO-EMULSIONS - STABLE PROTEIN-FREE ANALOGS OF LOW-DENSITY LIPOPROTEINS
    VIA, DP
    CRAIG, IF
    JACOBS, GW
    VANWINKLE, WB
    CHARLTON, SC
    GOTTO, AM
    SMITH, LC
    JOURNAL OF LIPID RESEARCH, 1982, 23 (04) : 570 - 576