Krusekopf Solveigh, Roots Ivar
Institute of Clinical Pharmacology, Charité Campus Mitte, Charité University Medical Center, Humboldt University of Berlin, Berlin, Germany.
Pharmacogenet Genomics. 2005 Nov;15(11):817-29. doi: 10.1097/01.fpc.0000175597.60066.3d.
The effects of St. John's wort and hyperforin on gene expression were analysed in HepG2 cells by Affymetrix microarray hybridization and real time reverse transcription-PCR.
Both compounds increased mRNAs of the drug metabolizing enzymes CYP3A4, CYP1A1, CYP1A2 and the flavin containing monooxygenase FMO5, and of the multidrug resistance protein MRP2. CYP4F2 and the reduced nicotinamide adenine dinucleotide dehydrogenase NQO1 were downregulated. Expression of genes mediating cholesterol biosynthesis was decreased, while facilitated glucose transporters and glycolysis genes were induced, indicating increased glucose metabolism. Changes of a considerable number of additional transcripts corresponded to reports on gene regulation by hypoxia. Endoplasmic reticulum stress-regulated genes involved in unfolded protein response and in protection of cells from apoptosis were downregulated. Other calcium binding proteins were affected by both treatments, suggesting an increase in intracellular calcium.
St. John's wort and hyperforin concordantly affected expression of genes not only mediating metabolism and transport of exogenous and endogenous compounds, but also involved in energy metabolism, intracellular calcium regulation, cell proliferation and apoptosis.
通过Affymetrix微阵列杂交和实时逆转录聚合酶链反应，分析圣约翰草及其主要成分金丝桃素对HepG2细胞基因表达的影响。
两种化合物均使药物代谢酶CYP3A4、CYP1A1、CYP1A2以及含黄素单加氧酶FMO5和多药耐药蛋白MRP2的mRNA水平升高。CYP4F2和还原型烟酰胺腺嘌呤二核苷酸脱氢酶NQO1表达下调。介导胆固醇生物合成的基因表达降低，而促进性葡萄糖转运蛋白和糖酵解基因被诱导，表明葡萄糖代谢增加。大量其他转录本的变化与缺氧相关基因调控的报道一致。参与未折叠蛋白反应和保护细胞免受凋亡的内质网应激调节基因表达下调。两种处理均影响其他钙结合蛋白，提示细胞内钙增加。
圣约翰草及其主要成分金丝桃素不仅协同影响介导外源性和内源性化合物代谢与转运的基因表达，还影响参与能量代谢、细胞内钙调节、细胞增殖和凋亡的基因表达。
