Abstract

Yeasts Saccharomyces cerevisiae, like other microbes in nature, respond to the unavailability of nutrients with entrance in quiescent/G₀ state. These cells exist in non-dividing, latent form by maintaining the cellular metabolism at a low level but still able to sense and adapt to environmental stresses. Their quiescent status characteristics are likely close to those of tissues and organs in mammals and humans. This fact makes them an appropriate model system for investigation of the basic mechanisms underlying the toxicity of different chemical compounds. In this study, the toxic effect of H₂O₂ and menadione on quiescent S. cerevisiae cells was evaluated through the analysis of RNA polymerases transcription profile and ribosomal RNA content. Distinct RNA polymerases subunits were expressed in G₀ yeast cells after short exposure to 0.1 mmol/L menadione and 5 mmol/L hydrogen peroxide. Significant transcription repression of RNA polymerases genes was observed as a response to menadione. Both stress agents induced changes in the 25S and 18S rRNA profile in quiescent and proliferating yeast cells. These results strongly suggest that the toxicological response of eukaryotic cells involves rapid alterations in RNA polymerases gene expression and changes in RNA transcriptome profiles, and depends on the specific mechanism of toxic action.

摘要

酵母酿酒酵母，像自然界中的其他微生物一样，以静止/G ₀状态进入，对营养物质的不可用性做出反应。这些细胞通过将细胞代谢维持在低水平而以非分裂的潜伏形式存在，但仍然能够感知和适应环境压力。它们的静止状态特征可能与哺乳动物和人类的组织和器官相似。这一事实使它们成为研究不同化合物毒性的基本机制的合适模型系统。在本研究中，H ₂ O ₂和甲萘醌对静止的酿酒酵母的毒性作用通过分析 RNA 聚合酶转录谱和核糖体 RNA 含量来评估细胞。短时间暴露于 0.1 mmol/L 甲萘醌和 5 mmol/L 过氧化氢后，不同的 RNA 聚合酶亚基在 G ₀酵母细胞中表达。观察到 RNA 聚合酶基因的显着转录抑制是对甲萘醌的反应。两种应激剂都能诱导静止和增殖酵母细胞中 25S 和 18S rRNA 谱的变化。这些结果强烈表明真核细胞的毒理学反应涉及 RNA 聚合酶基因表达的快速改变和 RNA 转录组谱的变化，并且取决于毒性作用的特定机制。