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首页> 外文期刊>BMC Medical Genomics >Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol
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Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol

机译：鉴定受白藜芦醇（天然白藜芦醇的二甲醚类似物）影响的分子途径

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Background Pterostilbene, a naturally occurring phenolic compound produced by agronomically important plant genera such as Vitis and Vacciunium , is a phytoalexin exhibiting potent antifungal activity. Additionally, recent studies have demonstrated several important pharmacological properties associated with pterostilbene. Despite this, a systematic study of the effects of pterostilbene on eukaryotic cells at the molecular level has not been previously reported. Thus, the aim of the present study was to identify the cellular pathways affected by pterostilbene by performing transcript profiling studies, employing the model yeast Saccharomyces cerevisiae . Methods S. cerevisiae strain S288C was exposed to pterostilbene at the IC50 concentration (70 μM) for one generation (3 h). Transcript profiling experiments were performed on three biological replicate samples using the Affymetrix GeneChip Yeast Genome S98 Array. The data were analyzed using the statistical methods available in the GeneSifter microarray data analysis system. To validate the results, eleven differentially expressed genes were further examined by quantitative real-time RT-PCR, and S. cerevisiae mutant strains with deletions in these genes were analyzed for altered sensitivity to pterostilbene. Results Transcript profiling studies revealed that pterostilbene exposure significantly down-regulated the expression of genes involved in methionine metabolism, while the expression of genes involved in mitochondrial functions, drug detoxification, and transcription factor activity were significantly up-regulated. Additional analyses revealed that a large number of genes involved in lipid metabolism were also affected by pterostilbene treatment. Conclusion Using transcript profiling, we have identified the cellular pathways targeted by pterostilbene, an analog of resveratrol. The observed response in lipid metabolism genes is consistent with its known hypolipidemic properties, and the induction of mitochondrial genes is consistent with its demonstrated role in apoptosis in human cancer cell lines. Furthermore, our data show that pterostilbene has a significant effect on methionine metabolism, a previously unreported effect for this compound.
机译：背景技术紫檀萜是一种由农学上重要的植物属（例如葡萄属和牛痘属）生产的天然酚类化合物，是一种具有较强抗真菌活性的植物抗毒素。另外，最近的研究已经证明了与蝶芪相关的几种重要药理性质。尽管如此，以前还没有关于在分子水平上对蕨类植物对真核细胞的作用进行系统研究的报道。因此，本研究的目的是通过使用酿酒酵母模型酵母进行转录谱分析研究来鉴定受蝶草烯影响的细胞途径。方法将酿酒酵母菌株S288C在IC 50 浓度（70μM）下暴露于紫檀皮中1代（3 h）。使用Affymetrix GeneChip酵母基因组S98阵列对三个生物学重复样品进行转录谱分析实验。使用GeneSifter微阵列数据分析系统中可用的统计方法分析数据。为了验证结果，通过定量实时RT-PCR进一步检查了11个差异表达的基因，并分析了在这些基因中缺失的酿酒酵母突变株对蝶呤的敏感性。结果转录谱分析研究表明，紫檀皮暴露显着下调蛋氨酸代谢相关基因的表达，而线粒体功能，药物排毒和转录因子活性相关基因的表达则显着上调。进一步的分析表明，蝶呤处理也影响大量参与脂质代谢的基因。结论使用转录谱分析，我们已经鉴定出了白藜芦醇类似物翼骨萜靶向的细胞途径。脂质代谢基因中观察到的反应与其已知的降血脂特性一致，线粒体基因的诱导与其在人癌细胞系中凋亡中的作用相一致。此外，我们的数据表明，蝶烯对蛋氨酸的代谢具有重要作用，这是该化合物先前未报道的作用。

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