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巨噬源性泡沫细胞中p62蛋白上调作用和机制的研究

林张军 李倩 章越凡 芮耀诚

林张军, 李倩, 章越凡, 芮耀诚. 巨噬源性泡沫细胞中p62蛋白上调作用和机制的研究[J]. 药学实践与服务, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004
引用本文: 林张军, 李倩, 章越凡, 芮耀诚. 巨噬源性泡沫细胞中p62蛋白上调作用和机制的研究[J]. 药学实践与服务, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004
LIN Zhangjun, LI Qian, ZHANG Yuefan, RUI Yaocheng. A study on the role and mechanism of upregulated p62 protein in macrophage-derived foam cells[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004
Citation: LIN Zhangjun, LI Qian, ZHANG Yuefan, RUI Yaocheng. A study on the role and mechanism of upregulated p62 protein in macrophage-derived foam cells[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004

巨噬源性泡沫细胞中p62蛋白上调作用和机制的研究

doi: 10.3969/j.issn.1006-0111.2019.05.004
基金项目: 国家自然科学基金(30672455)

A study on the role and mechanism of upregulated p62 protein in macrophage-derived foam cells

  • 摘要: 目的 探讨巨噬源性泡沫细胞中p62蛋白对脂质代谢相关的自噬以及炎症因子表达的影响,为p62在抗动脉粥样硬化中的应用提供参考。 方法 利用Ox-LDL刺激RAW264.7细胞的方法模拟巨噬源性泡沫细胞的形成,通过Western blot及实时荧光定量PCR检测巨噬源性泡沫细胞中p62蛋白和mRNA水平。通过Western blot比较p62 siRNA组和对照组中Ox-LDL诱导的LC3剪切、脂滴相关蛋白Plin2和过氧化物酶体相关蛋白PEX2的蛋白水平,通过实时荧光定量PCR比较TNFα和IL-6 mRNA表达水平。 结果 Ox-LDL对RAW264.7细胞中p62蛋白以及mRNA水平均有上调作用。干扰p62的表达之后,LC3-Ⅱ蛋白水平降低,Plin2的蛋白水平并无明显变化,PEX2的蛋白水平升高,TNFα和IL-6 mRNA表达升高。进一步研究发现,干扰Nrf2后能明显抑制Ox-LDL对p62的上调作用。 结论 巨噬源性泡沫细胞中Ox-LDL通过Nrf2介导p62蛋白的上调,p62可能具有抗动脉粥样硬化的作用。
  • [1] HANSSON G K.Inflammation,atherosclerosis,and coronary artery disease[J].N Engl J Med,2005,352(16):1685-1695.
    [2] LEVINE B,KROEMER G.Autophagy in the pathogenesis of disease[J].Cell,2008,132(1):27-42.
    [3] EVANS T D,SERGIN I,ZHANG X Y,et al.Target acquired:Selective autophagy in cardiometabolic disease[J].Sci Signal,2017,10(468):eaag2298.
    [4] OUIMET M,FRANKLIN V,MAK E,et al.Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase[J].Cell Metab,2011,13(6):655-667.
    [5] LIAO X H,SLUIMER J C,WANG Y,et al.Macrophage autophagy plays a protective role in advanced atherosclerosis[J].Cell Metab,2012,15(4):545-553.
    [6] LIPPAI M,LÖW P.The role of the selective adaptor p62 and ubiquitin-like proteins in autophagy[J].Biomed Res Int,2014,2014:832704.
    [7] MANLEY S,WILLIAMS J A,DING W X.Role of p62/SQSTM1 in liver physiology and pathogenesis[J].Exp Biol Med (Maywood),2013,238(5):525-538.
    [8] BITTO A,LERNER C A,NACARELLI T,et al.P62/SQSTM1 at the interface of aging,autophagy,and disease[J].Age (Dordr),2014,36(3):9626.
    [9] BURDELSKI C,REISWICH V,HUBE-MAGG C,et al.Cytoplasmic accumulation of sequestosome 1(p62) is a predictor of biochemical recurrence,rapid tumor cell proliferation,and genomic instability in prostate cancer[J].Clin Cancer Res,2015,21(15):3471-3479.
    [10] SERGIN I,BHATTACHARYA S,EMANUEL R,et al.Inclusion bodies enriched for p62 and polyubiquitinated proteins in macrophages protect against atherosclerosis[J].Sci Signal,2016,9(409):ra2.
    [11] SERGIN I,EVANS T D,ZHANG X Y,et al.Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis[J].Nat Commun,2017,8:15750.
    [12] GROOTAERT M O J,ROTH L,SCHRIJVERS D M,et al.Defective autophagy in atherosclerosis:to die or to senesce?[J].Oxid Med Cell Longev,2018,2018:7687083.
    [13] JEONG S J,ZHANG X Y,RODRIGUEZ-VELEZ A,et al.P62/SQSTM1 and selective autophagy in cardiometabolic diseases[J].Antioxid Redox Signal,2019,31(6):458-471.
    [14] HU D,WU J,XU L F,et al.A method for the establishment of a cell line with stable expression of the GFP-LC3 reporter protein[J].Mol Med Rep,2012,6(4):783-786.
    [15] LIU N,WU C M,SUN L Z,et al.Sesamin enhances cholesterol efflux in RAW264.7 macrophages[J].Molecules,2014,19(6):7516-7527.
    [16] GUPTA N,GOSWAMI R,ALHARBI M O,et al.TRPV 4 is a regulator in P.gingivalis lipopolysaccharide-induced exacerbation of macrophage foam cell formation[J].Physiol Rep,2019,7(7):e14069.
    [17] BIERMANNS M,VON LAAR J,BROSIUS U,et al.The peroxisomal membrane targeting elements of human peroxin 2(PEX2)[J].Eur J Cell Biol,2003,82(4):155-162.
    [18] ISHⅡ T,ITOH K,TAKAHASHI S,et al.Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages[J].J Biol Chem,2000,275(21):16023-16029.
    [19] PARK Y M.CD36,a scavenger receptor implicated in atherosclerosis[J].Exp Mol Med,2014,46:e99.DOI: 10.1038/emm.2014.38.
    [20] CHOROMANSKA B,MYSLIWIEC P,CHOROMANSKA K,et al.The role of CD36 receptor in the pathogenesis of atherosclerosis[J].Adv Clin Exp Med,2017,26(4):717-722.
    [21] JEONG S J,LEE M N,OH G T.The role of macrophage lipophagy in reverse cholesterol transport[J].Endocrinol Metab (Seoul),2017,32(1):41-46.
    [22] SANDA G M,DELEANU M,TOMA L,et al.Oxidized LDL-exposed human macrophages display increased MMP-9 expression and secretion mediated by endoplasmic reticulum stress[J].J Cell Biochem,2017,118(4):661-669.
    [23] YAO S T,MIAO C,TIAN H,et al.Endoplasmic reticulum stress promotes macrophage-derived foam cell formation by up-regulating cluster of differentiation 36(CD36) expression[J].J Biol Chem,2014,289(7):4032-4042.
    [24] NING H F,LIU D,YU X C,et al.Oxidized low-density lipoprotein-induced p62/SQSTM1 accumulation in THP-1-derived macrophages promotes IL-18 secretion and cell death[J].Exp Ther Med,2017,14(6):5417-5423.
    [25] KIM J Y,OZATO K.The sequestosome 1/p62 attenuates cytokine gene expression in activated macrophages by inhibiting IFN regulatory factor 8 and TNF receptor-associated factor 6/NF-kappaB activity[J].J Immunol,2009,182(4):2131-2140.
    [26] KIRKIN V,LAMARK T,JOHANSEN T,et al.NBR1 cooperates with p62 in selective autophagy of ubiquitinated targets[J].Autophagy,2009,5(5):732-733.
    [27] NIAN Z Q,SUN Z Q,YU L X,et al.Fat-specific protein 27 undergoes ubiquitin-dependent degradation regulated by triacylglycerol synthesis and lipid droplet formation[J].J Biol Chem,2010,285(13):9604-9615.
    [28] FUJIMOTO T,OHSAKI Y.Proteasomal and autophagic pathways converge on lipid droplets[J].Autophagy,2006,2(4):299-301.
    [29] OUIMET M,MARCEL Y L.Regulation of lipid droplet cholesterol efflux from macrophage foam cells[J].Arterioscler Thromb Vasc Biol,2012,32(3):575-581.
    [30] TILL A,LAKHANI R,BURNETT S F,et al.Pexophagy:the selective degradation of peroxisomes[J].Int J Cell Biol,2012,2012:512721.
    [31] SARGENT G,VAN ZUTPHEN T,SHATSEVA T,et al.PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation[J].J Cell Biol,2016,214(6):677-690.
    [32] JAIN A,LAMARK T,SJØTTEM E,et al.P62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription[J].J Biol Chem,2010,285(29):22576-22591.
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巨噬源性泡沫细胞中p62蛋白上调作用和机制的研究

doi: 10.3969/j.issn.1006-0111.2019.05.004
    基金项目:  国家自然科学基金(30672455)

摘要: 目的 探讨巨噬源性泡沫细胞中p62蛋白对脂质代谢相关的自噬以及炎症因子表达的影响,为p62在抗动脉粥样硬化中的应用提供参考。 方法 利用Ox-LDL刺激RAW264.7细胞的方法模拟巨噬源性泡沫细胞的形成,通过Western blot及实时荧光定量PCR检测巨噬源性泡沫细胞中p62蛋白和mRNA水平。通过Western blot比较p62 siRNA组和对照组中Ox-LDL诱导的LC3剪切、脂滴相关蛋白Plin2和过氧化物酶体相关蛋白PEX2的蛋白水平,通过实时荧光定量PCR比较TNFα和IL-6 mRNA表达水平。 结果 Ox-LDL对RAW264.7细胞中p62蛋白以及mRNA水平均有上调作用。干扰p62的表达之后,LC3-Ⅱ蛋白水平降低,Plin2的蛋白水平并无明显变化,PEX2的蛋白水平升高,TNFα和IL-6 mRNA表达升高。进一步研究发现,干扰Nrf2后能明显抑制Ox-LDL对p62的上调作用。 结论 巨噬源性泡沫细胞中Ox-LDL通过Nrf2介导p62蛋白的上调,p62可能具有抗动脉粥样硬化的作用。

English Abstract

林张军, 李倩, 章越凡, 芮耀诚. 巨噬源性泡沫细胞中p62蛋白上调作用和机制的研究[J]. 药学实践与服务, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004
引用本文: 林张军, 李倩, 章越凡, 芮耀诚. 巨噬源性泡沫细胞中p62蛋白上调作用和机制的研究[J]. 药学实践与服务, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004
LIN Zhangjun, LI Qian, ZHANG Yuefan, RUI Yaocheng. A study on the role and mechanism of upregulated p62 protein in macrophage-derived foam cells[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004
Citation: LIN Zhangjun, LI Qian, ZHANG Yuefan, RUI Yaocheng. A study on the role and mechanism of upregulated p62 protein in macrophage-derived foam cells[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(5): 400-405,426. doi: 10.3969/j.issn.1006-0111.2019.05.004
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