姜黄素对p210(bcr/abl)的下调作用涉及破坏热休克蛋白90（Hsp90）的分子伴侣功能。

Down-regulation of p210(bcr/abl) by curcumin involves disrupting molecular chaperone functions of Hsp90.

作者信息

Wu Li-Xian, Xu Jian-Hua, Huang Xiu-Wang, Zhang Kun-Zhong, Wen Cai-Xia, Chen Yuan-Zhong

机构信息

Institute of Clinical Pharmacology, Department of Pharmacology, Fujian Medical University, Fuzhou 350004, China.

出版信息

Acta Pharmacol Sin. 2006 Jun;27(6):694-9. doi: 10.1111/j.1745-7254.2006.00326.x.

DOI:10.1111/j.1745-7254.2006.00326.x

PMID:16723087

Abstract

AIM

To investigate the effects of curcumin (Cur) on p210(bcr/abl) level in K562 cells, and the relationship between these effects and the molecular chaperone functions of heat shock protein 90 (Hsp90).

METHODS

Flow cytometry and Western blot were used to examine the abundance of p210(bcr/abl), Hsp90, p23, Hsp70, and p60(Hop) in K562 cells treated with Cur. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the bcr-abl mRNA level in K562 cells treated with Cur. After co-immunoprecipitation of p210(bcr/abl) and its molecular chaperones, the immunoprecipitate was then subjected to Western blot analysis with anti-Hsp90, anti-Hsp70, anti-p23, and anti- p60(Hop)mAb.

RESULTS

An exposure of K562 cells to Cur produced time-dependent down-regulation of p210(bcr/abl), the inhibition rate of p210(bcr/abl) in K562 cells determined by flow cytometry after treatment with Cur 27.2 micromol/L for 1 h, 6 h, 12 h and 24 h was 31.2%, 63.7%, 81.3% and 94.5%, respectively. In contrast, Cur had almost no influence on bcr-abl mRNA level. Treatment with Cur for 24 h reduced the association of p210(bcr/abl) with Hsp90/p23 complex, while increasing the association of p210(bcr/abl) with Hsp70/ p60(Hop) complex; however, the total protein abundance of Hsp90, p23, and p60(Hop) in K562 cells had no apparent change, while Hsp70 increased greatly.

CONCLUSION

Down-regulation of p210(bcr/abl) by Cur involves dissociating the binding of p210(bcr/abl) with Hsp90/p23 complex. In contrast, the association of p210(bcr/abl) with Hsp70/ p60(Hop) complex increased.

摘要

目的

研究姜黄素（Cur）对K562细胞中p210（bcr/abl）水平的影响，以及这些影响与热休克蛋白90（Hsp90）分子伴侣功能之间的关系。

方法

采用流式细胞术和蛋白质免疫印迹法检测用Cur处理的K562细胞中p210（bcr/abl）、Hsp90、p23、Hsp70和p60（Hop）的丰度。采用逆转录聚合酶链反应（RT-PCR）测定用Cur处理的K562细胞中bcr-abl mRNA水平。对p210（bcr/abl）及其分子伴侣进行共免疫沉淀后，用抗Hsp90、抗Hsp70、抗p23和抗p60（Hop）单克隆抗体对免疫沉淀物进行蛋白质免疫印迹分析。

结果

K562细胞暴露于Cur后，p210（bcr/abl）呈时间依赖性下调，用27.2 μmol/L Cur处理1 h、6 h、12 h和24 h后，通过流式细胞术测定K562细胞中p210（bcr/abl）的抑制率分别为31.2%、63.7%、81.3%和94.5%。相比之下，Cur对bcr-abl mRNA水平几乎没有影响。用Cur处理24 h可降低p210（bcr/abl）与Hsp90/p23复合物的结合，同时增加p210（bcr/abl）与Hsp70/p60（Hop）复合物的结合；然而，K562细胞中Hsp90、p23和p60（Hop）的总蛋白丰度没有明显变化，而Hsp70显著增加。