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暴露于双酚A的酿酒酵母转录谱分析。

Analysis of transcriptional profiles of Saccharomyces cerevisiae exposed to bisphenol A.

作者信息

Bereketoglu Ceyhun, Arga Kazim Yalcin, Eraslan Serpil, Mertoglu Bulent

机构信息

Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.

Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, Gümüşhane University, Gümüşhane, Turkey.

出版信息

Curr Genet. 2017 May;63(2):253-274. doi: 10.1007/s00294-016-0633-z. Epub 2016 Jul 26.

Abstract

Bisphenol A (BPA), an endocrine disrupting chemical, is used as a monomer in the production of epoxy resins and polycarbonates, and as a plasticizer in polyvinyl chloride. As such, it is produced in large quantities worldwide and continuously leaches into the environment. To capture the genome reprogramming in eukaryotic cells under BPA exposure, here, we used Saccharomyces cerevisiae as model organism and analyzed the genome-wide transcriptional profiles of S. cerevisiae BY4742 in response to BPA, focusing on two exposure scenarios: (1) exposure to a low inhibition concentration (50 mg/L; resulting in <10 % inhibition in cell number) and (2) a high inhibition concentration (300 mg/L; resulting in >70 % inhibition in cell number). Based on the transcriptional profiling analyses, 81 genes were repressed and 104 genes were induced in response to 50 mg/L BPA. Meanwhile, 378 genes were downregulated and 606 genes were significantly upregulated upon exposure to 300 mg/L BPA. While similar processes were affected by exposure to distinct BPA concentrations, including mitochondrial processes, nucleobase-containing small molecule metabolic processes, transcription from the RNA polymerase II promoter, and mitosis and associated processes, the number and magnitude of differentially expressed genes differ between low and high inhibition concentration treatments. For example, exposure to 300 mg/L BPA resulted in severe changes in the expression levels of several genes involved in oxidative phosphorylation, the tricarboxylic acid cycle, ribosomal activity, replication, and chemical responses. Conversely, only slight changes were observed in the expression of genes involved in these processes in cells exposed to 50 mg/L BPA. These results demonstrate that yeast cells respond to BPA in a concentration-dependent manner at the transcriptional level via different genes and provide insight into the molecular mechanisms underlying the modes of action of BPA.

摘要

双酚A(BPA)是一种内分泌干扰化学物质,用作环氧树脂和聚碳酸酯生产中的单体,以及聚氯乙烯中的增塑剂。因此,它在全球大量生产并持续渗入环境。为了捕捉双酚A暴露下真核细胞中的基因组重编程,在此,我们使用酿酒酵母作为模式生物,分析了酿酒酵母BY4742响应双酚A的全基因组转录谱,重点关注两种暴露情况:(1)暴露于低抑制浓度(50mg/L;导致细胞数量抑制<10%)和(2)高抑制浓度(300mg/L;导致细胞数量抑制>70%)。基于转录谱分析,响应50mg/L双酚A时,81个基因被抑制,104个基因被诱导。同时,暴露于300mg/L双酚A时,378个基因下调,606个基因显著上调。虽然暴露于不同双酚A浓度会影响相似的过程,包括线粒体过程、含核碱基小分子代谢过程、RNA聚合酶II启动子的转录以及有丝分裂和相关过程,但低抑制浓度和高抑制浓度处理之间差异表达基因的数量和幅度不同。例如,暴露于300mg/L双酚A会导致参与氧化磷酸化、三羧酸循环、核糖体活性、复制和化学反应的几个基因的表达水平发生严重变化。相反,在暴露于50mg/L双酚A的细胞中,参与这些过程的基因表达仅观察到轻微变化。这些结果表明,酵母细胞在转录水平上通过不同基因以浓度依赖方式响应双酚A,并为双酚A作用模式的分子机制提供了见解。

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