Reinvestigation of the effect of carbenoxolone on the induction of heat shock proteins
Reinvestigation of the effect of carbenoxolone on the induction of heat shock proteins
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DOI：
10.1007/s12192-009-0106-0
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发表时间：
2009-09-01
影响因子：
3.8
通讯作者：
Ohtsuka, Kenzo
中科院分区：
文献类型：
--
作者：
Kawashima, Daisuke;Asai, Midori;Ohtsuka, Kenzo
甘珀酸（CBX）是甘草根物质甘草酸的半合成衍生物，并且先前已经报道仅诱导热休克蛋白70 [Hsp70，HSPA1A（根据最近的命名指南，热休克蛋白的系统名称在每个HSP之后的括号中给出，Kampinga等人，Cell Stress Chaperones，14：105 - 111，2008），而不是其它热休克蛋白（HSP）（Nagayama等人，life Sci. 69：2867 - 2873，2001）。在这项研究中，我们重新研究了CBX对HeLa和人神经母细胞瘤（A-172）细胞中热休克蛋白诱导的影响。CBX在10至800 μ M浓度下孵育16小时，不仅明显诱导Hsp70，而且诱导Hsp90（HSPC 1）、Hsp40（DNA JB 1）和Hsp27（HSPB 1）。然而，在更高的浓度（超过400 μ M），CBX似乎是有毒的。用CBX处理细胞导致热休克转录因子1（HSF 1）的磷酸化和DNA结合能力增强。此外，在细胞核中形成特征性的HSF1颗粒，表明CBX诱导HSPs是通过激活HSF1介导的。此外，热耐受性诱导CBX治疗，确定克隆生存。虽然目前尚不清楚CBX的确切靶点，但这些结果表明CBX是分子伴侣诱导剂之一，并表明CBX的某些药理活性可能部分归因于其分子伴侣诱导性质。
Carbenoxolone (CBX) is a semisynthetic derivative of the licorice root substance glycyrrhizinic acid and has been previously reported to induce only heat shock protein 70 [Hsp70, HSPA1A (the systematic name of heat shock protein is given in the parenthesis after each HSP, according to the recent nomenclature guidelines, Kampinga et al., Cell Stress Chaperones, 14:105-111, 2008) but not other heat shock proteins (HSPs) (Nagayama et al., Life Sci. 69:2867-2873, 2001). In this study, we reinvestigated the effect of CBX on the induction of HSPs in HeLa and human neuroblastoma (A-172) cells. CBX clearly induced not only Hsp70 but also Hsp90 (HSPC1), Hsp40 (DNAJB1), and Hsp27 (HSPB1) at concentrations of 10 to 800 mu M for 16 h incubation. At higher concentrations (more than 400 mu M), however, CBX appeared to be toxic. Treatment of cells with CBX resulted in enhanced phosphorylation and acquisition of DNA-binding ability of heat shock transcription factor 1 (HSF1). Furthermore, characteristic HSF1 granules were formed in the nucleus, suggesting that the induction of HSPs by CBX is mediated by the activation of HSF1. Furthermore, thermotolerance was induced by CBX treatment, as determined by clonogenic survival. Although the precise target of CBX is not known at present, these results indicate that CBX is one of the molecular chaperone inducers and suggest that some pharmacological activities of CBX might be ascribable in part to its molecular chaperone-inducing property.