Volume 36 Issue 3
May  2020
Turn off MathJax
Article Contents
Article Navigation >  Journal of Nanjing University of traditional Chinese Medicine  > 2020  >  36(3): 370-375
YANGJin-wei, ZHAOCan, LIUXiu, WUYong-jun, YURong. Effect of Zuogui Jiangtang Shuxin Formula Medicated Plasma on Foaming and Apoptosis of Macrophage Induced by ox-LDL Through PERK/ eIF2α/ATF4 Signaling Pathway[J]. Journal of Nanjing University of traditional Chinese Medicine, 2020, 36(3): 370-375.
Citation: YANGJin-wei, ZHAOCan, LIUXiu, WUYong-jun, YURong. Effect of Zuogui Jiangtang Shuxin Formula Medicated Plasma on Foaming and Apoptosis of Macrophage Induced by ox-LDL Through PERK/ eIF2α/ATF4 Signaling Pathway[J]. Journal of Nanjing University of traditional Chinese Medicine, 2020, 36(3): 370-375.
shu

Effect of Zuogui Jiangtang Shuxin Formula Medicated Plasma on Foaming and Apoptosis of Macrophage Induced by ox-LDL Through PERK/ eIF2α/ATF4 Signaling Pathway

  • 1.

    The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410208, China

  • 2.

    Graduate School, Hunan University of Chinese Medicine, Changsha, 410208, China

  • 3.

    Key Laboratory of Colleges and Universities, Traditional Chinese Medicine Prescription and Transformation of Medical Laboratory, Changsha, 410208, China

  • 4.

    School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China

  • Publish Date: 2020-05-10
    Abstract
  • OBJECTIVE To investigate the effect of Zuogui Jiangtang Shuxin Formula medicated plasma on ox-LDL-induced PERK/eIF2α/ATF4 integrated stress response and activation of apoptosis key signaling molecules CHOP and Caspase-12. METHEOD J774A.1 cells were randomly divided into 5 groups: normal group， model group， TUDCA group， Zuogui Jiangtang Shuxin Formula medicated plasma group and western medicine combination (metformin+atorvastatin calcium) medicated plasma group. All the drug intervention groups were pretreated with ox-LDL to establish an experimental model for macrophage foam cell formation. The cells of drug intervention groups were cultured in 10% different drug containing plasma， respectively. Cells of normal and model groups were cultured in normal culture medium. The growth inhibition of J774A.1 were tested by CCK-8 essay after 24 h culture. Oil Red O Dyeing experiment was used to show the cellular lipid droplets. The expression of p-PERK， p-eIF2α， ATF4， CHOP and Caspase-12 were detected by Western blot. RESULTS 100 mg/L ox-LDL suppressed the growth of J774A.1 cells with an inhibitory rate of (50.06±0.09)%. Oil Red O staining showed that the model group cells had more lipid droplets than normal group (P<0.01). Drug intervention groups effectively prevented the pervasion of ox-LDL to reduce lipid accumulation. Oil red O staining showed that lipid aggregated in Zuogui Jiangtang Shuxin Formula medicated plasma， compared with western medicine combination medicated plasma group (P<0.01)， and the effect was equivalent to TUDCA group (P＞0.05). ox-LDL up-regulated the expression of p-PERK， p-eIF2α， ATF4， CHOP and Caspase-12. Zuogui Jiangtang Shuxin Formula medicated plasma significantly restrained the expression of p-PERK， p-eIF2α and ATF4， and apparently decreased endoplasmic reticulum associated apoptosis protein CHOP and Caspase-12 expression (P<0.01). There was no significant difference in Zuogui Jiangtang Shuxin Formula medicated plasma group and TUDCA group. And Zuogui Jiangtang Shuxin Formula medicated plasma group was superior to the western medicine combination medicated plasma group (P<0.01). CONCLUSION Zuogui Jiangtang Shuxin Formula medicated plasma can suppress foam cell formation and apoptosis in J774A.1 cells， which may be related to the regulation of PERK/eIF2α/ATF4 signaling pathway and the expression of CHOP and Caspase-12.

     

    • FullText(HTML)
  • loading
    • References(19)
  • [1]
    COMINACINI L，GARBIN U，MOZZINI C，et al．The atherosclerotic plaque vulnerability：focus on the oxidative and endoplasmic Reticulum<\i> stress in orchestrating the macrophage apoptosis in the formation of the necrotic core[J]．Curr Med Chem，2015，22(13)：1565-1572．
    [2]
    KROPSKI JA，BLACKWELL TS．Endoplasmic Reticulum<\i> stress in the pathogenesis of fibrotic disease[J]．J Clin Invest，2018，128(1)：64-73．
    [3]
    AYAUB EA，KOLB PS，MOHAMMED-ALI Z，et al．GRP78 and CHOP modulate macrophage apoptosis and the development of bleomycin-induced pulmonary fibrosis[J]．J Pathol，2016，239(4)：411-425．
    [4]
    ABDULKARIM B，HERNANGOMEZ M，IGOILLO-ESTEVE M，et al．Guanabenz sensitizes pancreatic β cells to lipotoxic endoplasmic Reticulum<\i> stress and apoptosis[J]．Endocrinology，2017，158(6)：1659-1670．
    [5]
    成细华，喻嵘，吴勇军，等．左归降糖舒心方对转基因2型糖尿病MKR鼠心肌损伤的保护作用[J]．中草药，2011，42(2)：343-345．
    [6]
    成细华，喻嵘，黄政德，等．左归降糖舒心方对高脂饮食MKR小鼠糖脂代谢及炎症反应的影响[J]．中草药，2011，42(3)：546-549．
    [7]
    ESTRUCH M，MINAMBRES I，SANCHEZ-QUESADA JL，et al．Increased inflammatory effect of electronegative LDL and decreased protection by HDL in type 2 diabetic patients[J]．Atherosclerosis，2017，265：292-298．
    [8]
    WANG QL，ZHANG M，TORRES G，et al．Metformin suppresses diabetes-accelerated atherosclerosis via the inhibition of Drp1-mediated mitochondrial fission[J]．Diabetes，2017，66(1)：193-205．
    [9]
    WOLFFENBUTTEL BHR，SLAGTER SN，VAN WAATERINGE RP，et al．Unfavourable blood pressure and LDL-cholesterol levels in obese non-diabetic individuals[J]．Neth J Med，2017，75(9)：399-411．
    [10]
    WANG YC，DONG J，NIE J，et al．Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic Reticulum<\i> stress inhibition[J]．Apoptosis，2017，22(9)：1147-1156．
    [11]
    ZHOU XC，DONG SH，LIU ZS，et al．Regulation of gammaherpesvirus lytic replication by endoplasmic Reticulum<\i> stress-induced transcription factors ATF4 and CHOP[J]．J Biol Chem，2018，293(8)：2801-2814．
    [12]
    SOLANKI S，DUBE PR，TANO JY，et al．Reduced endoplasmic Reticulum<\i> stress-induced apoptosis and impaired unfolded protein response in TRPC3-deficient M1 macrophages[J]．Am J Physiol ，Cell Physiol，2014，307(6)：C521-C531．
    [13]
    YANG J，ZHANG X，YU XY，et al．Renin-angiotensin system activation accelerates atherosclerosis in experimental renal failure by promoting endoplasmic Reticulum<\i> stress-related inflammation[J]．Int J Mol Med，2017，39(3)：613-621．
    [14]
    VAN VLIET AR，GARG AD，AGOSTINIS P．Coordination of stress，Ca2+，and immunogenic signaling pathways by PERK at the endoplasmic Reticulum<\i>[J]．Biol Chem，2016，397(7)：649-656．
    [15]
    KAIRA K，TOYODA M，SHIMIZU A，et al．Expression of ER stress markers (GRP78/BiP and PERK) in adenoid cystic carcinoma[J]．Acta Otolaryngol，2016，136(1)：1-7．
    [16]
    CHANG HZ，CAI F，ZHANG Y，et al．Early-stage autophagy protects nucleus pulposus cells from glucose deprivation-induced degeneration via the p-eIF2α/ATF4 pathway[J]．Biomed Pharmacother，2017，89：529-535．
    [17]
    CHEN X，ZHONG JX，DONG DY，et al．Endoplasmic Reticulum<\i> stress-induced CHOP inhibits PGC-1α and causes mitochondrial dysfunction in diabetic embryopathy[J]．Toxicol Sci，2017，158(2)：275-285．
    [18]
    LI H，YU JS，ZHANG HS，et al．Increased expression of caspase-12 after experimental subarachnoid hemorrhage[J]．Neurochem Res，2016，41(12)：3407-3416．
    [19]
    ZHAO Y，JIANG CP，HE JH，et al．Multifunctional dextran sulfate-coated reconstituted high density lipoproteins target macrophages and promote beneficial antiatherosclerotic mechanisms[J]．Bioconjug Chem，2017，28(2)：438-448．
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索
    Get Citation
    PDF
    XML

    Article Metrics

    Article views (547) PDF downloads(367) Cited by()
    Proportional views
    Related

    Copyright © Journal of Nanjing University of traditional Chinese Medicine

    Sponsored by：Nanjing University of traditional Chinese MedicineAddress：No.138 xianlin Avenue, Qixia District, Nanjing cityChina Pos：210023

    Tel：025-85811935Email：xb@njucm.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return