Yan Dai, Saito Kiyoto, Ohmi Yuri, Fujie Noriyo, Ohtsuka Kenzo
Laboratory of Cell and Stress Biology, Department of Environmental Biology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
Cell Stress Chaperones. 2004 Winter;9(4):378-89. doi: 10.1379/csc-51r.1.
Heat shock proteins (HSPs) are induced by various physical, chemical, and biological stresses. HSPs are known to function as molecular chaperones, and they not only regulate various processes of protein biogenesis but also function as lifeguards against proteotoxic stresses. Because it is very useful to discover nontoxic chaperone-inducing compounds, we searched for them in herbal medicines. Some herbal medicines had positive effects on the induction of HSPs (Hsp70, Hsp40, and Hsp27) in cultured mammalian cells. We next examined 2 major constituents of these herbal medicines, glycyrrhizin and paeoniflorin, with previously defined chemical structures. Glycyrrhizin had an enhancing effect on the HSP induction by heat shock but could not induce HSPs by itself. In contrast, paeoniflorin had not only an enhancing effect but also an inducing effect by itself on HSP expression. Thus, paeoniflorin might be termed a chaperone inducer and glycyrrhizin a chaperone coinducer. Treatment of cells with paeoniflorin but not glycyrrhizin resulted in enhanced phosphorylation and acquisition of the deoxyribonucleic acid-binding ability of heat shock transcription factor 1 (HSF1), as well as the formation of characteristic HSF1 granules in the nucleus, suggesting that the induction of HSPs by paeoniflorin is mediated by the activation of HSF1. Also, thermotolerance was induced by treatment with paeoniflorin but not glycyrrhizin. Paeoniflorin had no toxic effect at concentrations as high as 80 microg/ mL (166.4 microM). To our knowledge, this is the first report on the induction of HSPs by herbal medicines.
热休克蛋白（HSPs）可由各种物理、化学和生物应激诱导产生。已知HSPs作为分子伴侣发挥作用，它们不仅调节蛋白质生物合成的各种过程，还作为抗蛋白毒性应激的保护者发挥作用。由于发现无毒的伴侣诱导化合物非常有用，我们在草药中进行了寻找。一些草药对培养的哺乳动物细胞中HSPs（Hsp70、Hsp40和Hsp27）的诱导具有积极作用。接下来，我们研究了这些草药的两种主要成分，即具有先前确定化学结构的甘草酸和芍药苷。甘草酸对热休克诱导HSPs具有增强作用，但自身不能诱导HSPs。相比之下，芍药苷不仅具有增强作用，还能自身诱导HSPs表达。因此，芍药苷可被称为伴侣诱导剂，甘草酸可被称为伴侣共诱导剂。用芍药苷而非甘草酸处理细胞会导致热休克转录因子1（HSF1）的磷酸化增强和脱氧核糖核酸结合能力的获得，以及细胞核中特征性HSF1颗粒的形成，这表明芍药苷诱导HSPs是由HSF1的激活介导的。此外，芍药苷处理可诱导耐热性，而甘草酸则不能。芍药苷在高达80μg/mL（166.4μM）的浓度下没有毒性作用。据我们所知，这是关于草药诱导HSPs的首次报道。
