发表状态 | 已发表Published |
题名 | Phorbol 12-myristate 13-acetate promotes nuclear translocation of hepatic steroid response element binding protein-2 |
作者 | |
发表日期 | 2016-06-01 |
发表期刊 | International Journal of Biochemistry and Cell Biology
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ISSN/eISSN | 1357-2725 |
卷号 | 75页码:1-10 |
摘要 | Sterol regulatory element-binding protein (SREBP)-2 is a pivotal transcriptional factor in cholesterol metabolism. Factors interfering with the proper functioning of SREBP-2 potentially alter plasma lipid profiles. Phorbol 12-myristate 13-acetate (PMA), which is a common protein kinase C (PKC) activator, was shown to promote the post-translational processing and nuclear translocation of SREBP-2 in hepatic cells in the current study. Following SREBP-2 translocation, the transcripts of its target genes HMGCR and LDLR were upregulated as demonstrated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Electrophoretic mobility shift assays (EMSA) also demonstrated an induced DNA-binding activity on the sterol response element (SRE) domain under PMA treatment. The increase of activated Srebp-2 without the concurrent induced mRNA expression was also observed in an animal model. As the expression of SREBP-2 was not increased by PMA, the activation of PKC was the focus of investigation. Specific PKC isozyme inhibition and overexpression supported that PKCβ was responsible for the promoting effect. Further studies showed that the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK), but not 5′ adenosine monophosphate-activated protein kinase (AMPK), were the possible downstream signaling proteins of PKCβ. In conclusion, this study illustrated that PKCβ increased SREBP-2 nuclear translocation in a pathway mediated by MEK/ERK and JNK, rather than the one dictated by AMPK. These results revealed a novel signaling target of PKCβ in the liver cells. |
关键词 | Liver Phorbol ester PKC SREBP-2 |
DOI | 10.1016/j.biocel.2016.03.010 |
URL | 查看来源 |
收录类别 | SCIE |
语种 | 英语English |
WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
WOS类目 | Biochemistry & Molecular Biology ; Cell Biology |
WOS记录号 | WOS:000376832600001 |
Scopus入藏号 | 2-s2.0-84962702878 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://repository.uic.edu.cn/handle/39GCC9TT/13178 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Leung, Lai K. |
作者单位 | 1.Food and Nutritional Sciences/Biochemistry Programme,School of Life Sciences,Faculty of Science,Chinese University of Hong Kong,Shatin,Rm.507CMMW Bldg.,Hong Kong 2.Biochemistry Programmes,School of Life Sciences,Faculty of Science,Chinese University of Hong Kong,Shatin,Hong Kong 3.Dept. of Food Science,National Chiayi University,Chiayi City,Taiwan 4.Department of Chemistry,Faculty of Science,HongKong Baptist University,Kowloon Tong,Kowloon,Hong Kong |
推荐引用方式 GB/T 7714 | Wong, Tsz Yan,Tan, Yan Qin,Lin, Shu Meiet al. Phorbol 12-myristate 13-acetate promotes nuclear translocation of hepatic steroid response element binding protein-2[J]. International Journal of Biochemistry and Cell Biology, 2016, 75: 1-10. |
APA | Wong, Tsz Yan, Tan, Yan Qin, Lin, Shu Mei, & Leung, Lai K. (2016). Phorbol 12-myristate 13-acetate promotes nuclear translocation of hepatic steroid response element binding protein-2. International Journal of Biochemistry and Cell Biology, 75, 1-10. |
MLA | Wong, Tsz Yan,et al."Phorbol 12-myristate 13-acetate promotes nuclear translocation of hepatic steroid response element binding protein-2". International Journal of Biochemistry and Cell Biology 75(2016): 1-10. |
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