PMID- 28275300 OWN - NLM STAT- MEDLINE DCOM- 20170814 LR - 20181113 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 23 IP - 7 DP - 2017 Feb 21 TI - Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway. PG - 1203-1214 LID - 10.3748/wjg.v23.i7.1203 [doi] AB - AIM: To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS: HSC-T6 cells were cultured in vitro and 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 cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on alpha-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 cultured in 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. CONCLUSION: CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway. FAU - Yang, Ning AU - Yang N AD - 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. FAU - Shi, Juan-Juan AU - Shi JJ AD - 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. FAU - Wu, Feng-Ping AU - Wu FP AD - 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. FAU - Li, Mei AU - Li M AD - 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. FAU - Zhang, Xin AU - Zhang X AD - 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. FAU - Li, Ya-Ping AU - Li YP AD - 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. FAU - Zhai, Song AU - Zhai S AD - 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. FAU - Jia, Xiao-Li AU - Jia XL AD - 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. FAU - Dang, Shuang-Suo AU - Dang SS AD - 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. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Antioxidants) RN - 0 (Caffeic Acids) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Reactive Oxygen Species) RN - 339NCG44TV (Phenol) RN - G960R9S5SK (caffeic acid phenethyl ester) RN - ML9LGA7468 (Phenylethyl Alcohol) SB - IM MH - Animals MH - Antioxidants/*chemistry MH - Apoptosis MH - Caffeic Acids/*therapeutic use MH - Cell Line, Tumor MH - Cell Proliferation MH - Flow Cytometry MH - Hepatic Stellate Cells/*drug effects/metabolism MH - Immunoenzyme Techniques MH - *MAP Kinase Signaling System MH - Microscopy, Fluorescence MH - NF-E2-Related Factor 2/*metabolism MH - Oxidative Stress MH - Phenol MH - Phenylethyl Alcohol/*analogs & derivatives/therapeutic use MH - Protein Transport MH - Rats MH - Reactive Oxygen Species/metabolism PMC - PMC5323445 OTO - NOTNLM OT - Antioxidation OT - Caffeic acid phenethyl ester OT - Liver fibrosis OT - Mitogen activated protein kinases OT - Nrf2 COIS- Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists. EDAT- 2017/03/10 06:00 MHDA- 2017/08/15 06:00 PMCR- 2017/02/21 CRDT- 2017/03/10 06:00 PHST- 2016/11/15 00:00 [received] PHST- 2016/12/27 00:00 [revised] PHST- 2017/01/11 00:00 [accepted] PHST- 2017/03/10 06:00 [entrez] PHST- 2017/03/10 06:00 [pubmed] PHST- 2017/08/15 06:00 [medline] PHST- 2017/02/21 00:00 [pmc-release] AID - 10.3748/wjg.v23.i7.1203 [doi] PST - ppublish SO - World J Gastroenterol. 2017 Feb 21;23(7):1203-1214. doi: 10.3748/wjg.v23.i7.1203.