Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region

Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region
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DOI:
10.1038/tpj.2011.24
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发表时间:
2012-10-01
影响因子:
2.8
通讯作者:
Davies, G. E.
Davies, G. E.
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Y.;Ehli, E. A.;Davies, G. E.

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本研究的目的是研究小檗碱和吴茱萸碱对5-羟色胺转运体(5-HTT)表达的影响,然后测试如何等位基因的变化,以前确定的启动子区域可以调节这种影响在肾上腺素能神经元细胞系RN 46 A。小檗碱和吴茱萸碱,单独和组合,增加5-HTT mRNA和蛋白质的表达显着跨越各种等位基因。当分别针对S、XS 11、L-G、L-A、XL 17和XL 18等位基因进行测试时,100 μ M小檗碱使5-HTT启动子活性增加67%、128.7%、106.9%、100.4%、26.2%和82%,2 μ M吴茱萸碱使5-HTT启动子活性增加216.7%、81.6%、305.6%,分别为181.5%、175.3%和102.2%。小檗碱和吴茱萸碱增加5-HTT启动子活性的不同取决于5-HTTLPR多态性的遗传变异。这项研究提供了一个令人信服的例子,说明草药化合物如何影响研究最深入的精神病候选基因之一--血清素转运蛋白的表达。The Pharmacogenomics Journal(2012)12,372-378; doi:10.1038/tpj.2011.24; 2011年6月7日在线发表
The aim of this study was to investigate the effect of berberine and evodiamine on serotonin transporter (5-HTT) expression and then test how allelic variations previously identified in the promoter region could modulate that effect in the serotonergic neuronal cell line RN46A. Both berberine and evodiamine, alone and in combination, increased 5-HTT mRNA and protein expression significantly across the various alleles. When tested against the S, XS11, L-G, L-A, XL17, and XL18 alleles, respectively, 100 mu M berberine increased 5-HTT promoter activities by 67%, 128.7%, 106.9%, 100.4%, 26.2% and 82%, 2 mu M evodiamine increased 5-HTT promoter activities by 216.7%, 81.6%, 305.6%, 181.5%, 175.3% and 102.2%. Berberine and evodiamine increased 5-HTT promoter activity differently depending on the genetic variation of the 5-HTTLPR polymorphism. This study has provided a convincing example of how herbal compounds influence the expression of one of the most intensively studied psychiatric candidate genes, the serotonin transporter. The Pharmacogenomics Journal (2012) 12, 372-378; doi:10.1038/tpj.2011.24; published online 7 June 2011