Curcumin affects gene expression and reactive oxygen species via a PKA dependent mechanism in Dictyostelium discoideum. Dictyostelium discoideum

Botanicals are widely used as dietary supplements and for the prevention and treatment of disease. Despite a long history of use, there is generally little evidence supporting the efficacy and safety of these preparations. Curcumin has been used to treat a myriad of human diseases and is widely advertised and marketed for its ability to improve health, but there is no clear understanding how curcumin interacts with cells and affects cell physiology. D. discoideum is a simple eukaryotic lead system that allows both tractable genetic and biochemical studies. The studies reported here show novel effects of curcumin on cell proliferation and physiology, and a pleiotropic effect on gene transcription. Transcriptome analysis showed that the effect is two-phased with an early transient effect on the transcription of approximately 5% of the genome, and demonstrates that cells respond to curcumin through a variety of previously unknown molecular pathways. This is followed by later unique transcriptional changes and a protein kinase A dependent decrease in catalase A and three superoxide dismutase enzymes. Although this results in an increase in reactive oxygen species (ROS; superoxide and H2O2), the effects of curcumin on transcription do not appear to be the direct result of oxidation. This study opens the door to future explorations of the effect of curcumin on cell physiology. Overall design: Total 48 samples were used for this analysis. Transcriptomes of AX4 strain treated with curcumin at multiple concentrations (0, 2.5, 5.0, 7.5 and 10.0 µg/ml) for different durations (0, 4, 8 and 12 hour) were analyzed with 3 biological replicates.

植物药（Botanicals）被广泛用作膳食补充剂，同时也用于疾病的预防与治疗。尽管已有悠久的应用历史，但目前鲜有科学证据能够支撑这类制剂的有效性与安全性。姜黄素（Curcumin）已被用于治疗多种人类疾病，且因宣称的健康改善功效被广泛推广与销售，但目前仍未明确其与细胞相互作用、调控细胞生理活动的具体机制。盘基网柄菌（D. discoideum）是一种简单的真核模式研究系统，可用于开展可控的遗传与生化研究。
本研究报道了姜黄素对细胞增殖与生理活动的新型调控效应，以及其对基因转录的多效性影响。转录组（transcriptome）分析显示，该调控效应具有双时相特征：早期会对约5%的基因组转录产生瞬时影响，研究证实细胞可通过多种此前未被探明的分子通路响应姜黄素处理；后续则会出现独特的转录组改变，并伴随蛋白激酶A（protein kinase A）依赖的过氧化氢酶A与三种超氧化物歧化酶表达下调。尽管这一变化会导致活性氧（reactive oxygen species, ROS；超氧阴离子与过氧化氢H₂O₂）水平升高，但姜黄素对转录的调控效应并非由氧化应激直接介导。本研究为后续探索姜黄素对细胞生理的影响开辟了全新方向。
整体实验设计：本分析共纳入48份样本。对AX4菌株分别以不同浓度（0、2.5、5.0、7.5及10.0 µg/ml）的姜黄素处理不同时长（0、4、8及12小时），并设置3次生物学重复，随后对其转录组进行测序分析。