Comprehensive study in the inhibitory effect of berberine on gene transcription, including TATA box.
Comprehensive study in the inhibitory effect of berberine on gene transcription, including TATA box.
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小檗碱对基因转录抑制作用的综合研究，包括TATA Box
DOI：
10.1371/journal.pone.0023495
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Du L
中科院分区：
文献类型：
--
作者：
Wang Y;Kheir MM;Chai Y;Hu J;Xing D;Lei F;Du L
小檗碱（BBR）是一种天然的DNA嵌入剂，具有多种药理作用。然而，目前既没有关于这种生物碱在活细胞中的分布的详细报道，也没有关于BBR与DNA的缔合和DNA功能之间的关系的报道。在这里，我们报告说，给药后30分钟即可观察到BBR在细胞核内的分布，并且细胞核中小檗碱的含量在4 µmol左右达到峰值，即给药后12小时。DNA和染色质的空间构象改变后，立即与BBR协会。此外，这种缔合可以有效地抑制活细胞系统和无细胞系统中的DNA转录。电泳迁移率变动分析（EMSA）进一步证明BBR可以抑制TATA结合蛋白（TBP）与启动子中TATA盒的结合，这一发现也在活细胞中通过染色质免疫沉淀（ChIP）得到。基于本研究的结果，我们推测小檗碱可以抑制活细胞系统中DNA的转录，特别是通过与DNA结合来抑制TBP和TATA盒之间的关联，从而以非特异性方式抑制TATA盒依赖性基因的表达。这项新的研究显着扩大了有关黄连素的药理作用的知识范围，从其与TATA盒的最重要的初始相互作用开始。
Berberine (BBR) is an established natural DNA intercalator with numerous pharmacological functions. However, currently there are neither detailed reports concerning the distribution of this alkaloid in living cells nor reports concerning the relationship between BBR's association with DNA and the function of DNA. Here we report that the distribution of BBR within the nucleus can be observed 30 minutes after drug administration, and that the content of berberine in the nucleus peaks at around 4 µmol, which is twelve hours after drug administration. The spatial conformation of DNA and chromatin was altered immediately after their association with BBR. Moreover, this association can effectively suppress the transcription of DNA in living cell systems and cell-free systems. Electrophoretic mobility shift assays (EMSA) demonstrated further that BBR can inhibit the association between the TATA binding protein (TBP) and the TATA box in the promoter, and this finding was also attained in living cells by chromatin immunoprecipitation (ChIP). Based on results from this study, we hypothesize that berberine can suppress the transcription of DNA in living cell systems, especially suppressing the association between TBP and the TATA box by binding with DNA and, thus, inhibiting TATA box-dependent gene expression in a non-specific way. This novel study has significantly expanded the sphere of knowledge concerning berberine's pharmacological effects, beginning at its paramount initial interaction with the TATA box.
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影响因子：
56.9
作者：
BLOBEL, G;POTTER, VR
通讯作者：
POTTER, VR
DOI：
10.1016/j.bbagen.2008.05.005
发表时间：
2008-09-01
影响因子：
3
作者：
Bhadra, Kakali;Maiti, Motilal;Kumar, Gopinatha Suresh
通讯作者：
Kumar, Gopinatha Suresh
影响因子：
2.5
作者：
Wang, XL;Xing, DM;Du, LJ
通讯作者：
Du, LJ
小檗碱对小鼠的急性毒性及其与血药浓度的相关性
影响因子：
4.3
作者：
Kheir, Michael M.;Wang, Yugang;Dua, Lijun
通讯作者：
Dua, Lijun
影响因子：
2.9
作者：
CHIANG, SY;WELCH, J;BEERMAN, TA
通讯作者：
BEERMAN, TA