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

作　　者：Li-xian WU Jian-hua XU Xiu-wang HUANG Kun-zhong ZHANG Cai-xia WEN Yuan-zhong CHEN 

机构地区：[1]不详 [2]Institute of Clinical Pharmacology, Department of Pharmacology, Fujian Medical University [3]Fujian Institute of Hematology, Fuzhou 350004, China

出　　处：《Acta Pharmacologica Sinica》2006年第6期694-699,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(№30171158 and №30472187);the Natural Science Foundation of Fujian Province,China(№ C992001).

摘　　要：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^HoPmAb. 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 μmol/L for 1 h, 6h, 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.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^HoPmAb. 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 μmol/L for 1 h, 6h, 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.

关 键 词：CURCUMIN molecular chaperones bcr-abl fusion proteins heat shock protein 90 

分 类 号：Q51[生物学—生物化学]