Graduate School of Frontier Biosciences, Osaka University Suita, Osaka, Japan.
Graduate School of Natural Science, Konan University, Kobe, Hyogo, Japan.
Sci Rep. 2024 Mar 5;14(1):5401. doi: 10.1038/s41598-024-55794-z.
Temperature is a vital environmental factor affecting organisms' survival as they determine the mechanisms to tolerate rapid temperature changes. We demonstrate an experimental system for screening chemicals that affect cold tolerance in Caenorhabditis elegans. The anticancer drugs leptomycin B and camptothecin were among the 4000 chemicals that were screened as those affecting cold tolerance. Genes whose expression was affected by leptomycin B or camptothecin under cold stimuli were investigated by transcriptome analysis. Abnormal cold tolerance was detected in several mutants possessing genes that were rendered defective and whose expression altered after exposure to either leptomycin B or camptothecin. The genetic epistasis analysis revealed that leptomycin B or camptothecin may increase cold tolerance by affecting a pathway upstream of the insulin receptor DAF-2 that regulates cold tolerance in the intestine. Our experimental system combining drug and cold tolerance could be used for a comprehensive screening of genes that control cold tolerance at a low cost and in a short time period.
温度是影响生物体生存的重要环境因素，因为它决定了生物体耐受快速温度变化的机制。我们展示了一种用于筛选影响秀丽隐杆线虫耐寒性的化学物质的实验系统。在筛选的 4000 种化学物质中，有抗癌药物莱普霉素 B 和喜树碱。通过转录组分析研究了在冷刺激下受莱普霉素 B 或喜树碱影响表达的基因。在暴露于莱普霉素 B 或喜树碱后，其表达发生改变并出现异常耐寒性的几种突变体中，存在基因缺陷。遗传上位性分析表明，莱普霉素 B 或喜树碱可能通过影响调控肠道耐寒性的胰岛素受体 DAF-2 的上游途径来增加耐寒性。我们的实验系统结合了药物和耐寒性，可以在低成本和短时间内进行全面筛选控制耐寒性的基因。
