title: Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6viaan Nrf2-mediated mitogen activated protein kinases pathway.
abstract: OBJECTIVE
  To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells culturedin vitroand the potential mechanisms.
  
  
  METHODS
  HSC-T6 cells were culturedin vitroand treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells culturedin vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on α-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively.
  
  
  RESULTS
  CAPE inhibited the proliferation and activation of HSC-T6 cells culturedin vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors.
  
  
  CONCLUSIONS
  CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Shi
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Wu
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Li
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhai
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Jia
authors.affiliation: Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors.forename: Shuang-Suo
authors.initials: SS
authors.lastname: Dang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D017209:Apoptosis; D002109:Caffeic Acids / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D019800:Phenol; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D021381:Protein Transport; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D019800:Phenol; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Antioxidation; Caffeic acid phenethyl ester; Liver fibrosis; Mitogen activated protein kinases; Nrf2