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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
ISSN/eISSN1357-2725
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
DOI10.1016/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
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
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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