Naringenin ameliorates insulin resistance by modulating endoplasmic reticulum stress in hepatitis C virus-infected liver

被引:12
作者
Jia, Benli [1 ]
Wang, Yong [1 ]
Yu, Gang [1 ]
Cheng, Yunsheng [1 ]
Yang, Chuang [1 ]
Cao, Feng [1 ]
He, Yan [1 ]
Cao, Pengwei [1 ]
Meng, Xiangling [5 ]
Yu, Dongsheng [2 ,3 ,4 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 2, Dept Gen Surg, 678 Furong Rd, Hefei 230601, Anhui, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Tradit Chinese Med, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Zhengzhou 450052, Henan, Peoples R China
[4] Henan Key Lab Digest Organ Transplantat, Zhengzhou 450052, Henan, Peoples R China
[5] Anhui Med Univ, Affiliated Hosp 1, Dept Gen Surg, 81 Meishan Rd, Hefei 230022, Anhui, Peoples R China
关键词
HCV core protein; Naringenin; ER stress; IRE1; alpha; Insulin resistance; ER STRESS; EXPRESSION; ROLES; GRP78;
D O I
10.1016/j.biopha.2019.108848
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hepatitis C virus (HCV) infection may lead to hepatic insulin resistance (IR), and endoplasmic reticulum (ER) stress has been found to induce IR. In our previous study, naringenin (NGEN) had an insulin sensitization effect on the HCV core protein (HCVCP) infected mouse livers. In the present study, we examined the effects of NGEN on HCVCP infection-induced ER stress and investigated the insulin sensitization mechanism involved. We found that XBP1s was up-regulated in the livers of HCV-infected patients, in hepatocytes with HCV infection, and in HCVCP-infected mice. HCVCP induces ER stress in the mouse liver and hepatocytes by increasing XBP1s and downstream gene expression. Pre-treatment with NGEN inhibited the ER stress and downstream gene expression both in vivo and in vitro. Similar to the HCVCP infection results, NGEN also inhibited the ER stress in tunicamycin-treated Huh-7.5.1 cells. In addition, the role of IRE1 alpha in HCVCP-induced IR was detected, and knockdown of IRE1 alpha abolished HCVCP-stimulated IR. Overexpression induced IR but could be abolished by NGEN. NGEN also blocked the HCVCP-induced IRE1 alpha expression levels that were up-regulated in vivo. Our data reveal that ER stress may be associated with HCV-induced IR, and NGEN treatment inhibited ER stress activity and increased insulin sensitivity by decreasing the expression of IRE1 alpha.
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页数:8
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共 27 条
  • [1] Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion
    Benali-Furet, NL
    Chami, M
    Houel, L
    De Giorgi, F
    Vernejoul, F
    Lagorce, D
    Buscail, L
    Bartenschlager, R
    Ichas, F
    Rizzuto, R
    Paterlini-Bréchot, P
    [J]. ONCOGENE, 2005, 24 (31) : 4921 - 4933
  • [2] Protein Folding and Modification in the Mammalian Endoplasmic Reticulum
    Braakman, Ineke
    Bulleid, Neil J.
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, VOL 80, 2011, 80 : 71 - 99
  • [3] HCV induces transforming growth factor β1 through activation of endoplasmic reticulum stress and the unfolded protein response
    Chusri, Pattranuch
    Kumthip, Kattareeya
    Hong, Jian
    Zhu, Chuanlong
    Duan, Xiaoqiong
    Jilg, Nikolaus
    Fusco, Dahlene N.
    Brisac, Cynthia
    Schaefer, Esperance A.
    Cai, Dachuan
    Peng, Lee F.
    Maneekarn, Niwat
    Lin, Wenyu
    Chung, Raymond T.
    [J]. SCIENTIFIC REPORTS, 2016, 6
  • [4] Groepper C, 2018, J HEPATOL, V69, P594, DOI 10.1016/j.jhep.2018.04.005
  • [5] Imatinib Mesylate Reduces Endoplasmic Reticulum Stress and Induces Remission of Diabetes in db/db Mice
    Han, Myoung Sook
    Chung, Kun Wook
    Cheon, Hyae Gyeong
    Dal Rhee, Sang
    Yoon, Chang-Hwan
    Lee, Moon-Kyu
    Kim, Kwang-Won
    Lee, Myung-Shik
    [J]. DIABETES, 2009, 58 (02) : 329 - 336
  • [6] Endoplasmic Reticulum Stress and Inflammation in Obesity and Diabetes
    Hummasti, Sarah
    Hotamisligil, Goekhan S.
    [J]. CIRCULATION RESEARCH, 2010, 107 (05) : 579 - 591
  • [7] Naringenin improve hepatitis C virus infection induced insulin resistance by increase PTEN expression via p53-dependent manner
    Jia, Benli
    Yu, Dongsheng
    Yu, Gang
    Cheng, Yunsheng
    Wang, Yang
    Yi, Xiaoqiang
    Li, Xiaoping
    Wang, Yong
    [J]. BIOMEDICINE & PHARMACOTHERAPY, 2018, 103 : 746 - 754
  • [8] Physical exercise alleviates ER stress in obese humans through reduction in the expression and release of GRP78 chaperone
    Khadir, Abdelkrim
    Kavalakatt, Sina
    Abubaker, Jehad
    Cherian, Preethi
    Madhu, Dhanya
    Al-Khairi, Irina
    Abu-Farha, Mohamed
    Warsame, Sarnia
    Elkum, Naser
    Dehbi, Mohammed
    Tiss, Ali
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 2016, 65 (09): : 1409 - 1420
  • [9] The Roles of Endoplasmic Reticulum Overload Response Induced by HCV and NS4B Protein in Human Hepatocyte Viability and Virus Replication
    Kong, Lingbao
    Li, Shanshan
    Huang, Mingjie
    Xiong, Ying
    Zhang, Qinghua
    Ye, Li
    Liu, Jing
    Zhu, Xiangdong
    Sun, Ruina
    Guo, Yunli
    [J]. PLOS ONE, 2015, 10 (04):
  • [10] The Adaptive Endoplasmic Reticulum Stress Response to Lipotoxicity in Progressive Human Nonalcoholic Fatty Liver Disease
    Lake, April D.
    Novak, Petr
    Hardwick, Rhiannon N.
    Flores-Keown, Brieanna
    Zhao, Fei
    Klimecki, Walter T.
    Cherrington, Nathan J.
    [J]. TOXICOLOGICAL SCIENCES, 2014, 137 (01) : 26 - 35