Natural Compound Curcumin—a Channel Potentiator Rather Than a Corrector of the Defective Intracellular Processing of △F508 Mutant Cystic Fibrosis Transmembrane Conductance Regulator  

作　　者：LIU Xin GUAN Li HE Cheng-yan ZHANG Xiao-jing XU Li-na SHANG De-jing MA Tong-hui YANG Hong 

机构地区：[1]Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, P. R. China [2]China-Japan Union Hospital, Jilin University, Changchun 130033, P. R. China [3]Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029, P. R. China

出　　处：《Chemical Research in Chinese Universities》2008年第2期200-203,共4页高等学校化学研究（英文版）

基　　金：Supported by the National Natural Science Foundation for Distinguished Young Scholars(No30325011);National Natural Science Foundation of China(Nos30570864 and 30670477);Program for New Century Excellent Talents in University(No NCET-07-0406)

摘　　要：Cystic fibrosis（CF） is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator（CFTR） chloride channel. The most common point mutation AF508, which leads to impaired intracellular processing and channel gating of CFTR, appears in about 90% CF patients. The natural compound curcumin was reported to correct the processing defect of AF508-CFTR and proposed as a potential therapeutic drug to cure CF. In the present study, we analyzed the effect of curcumin on AF508-CFTR and demonstrated that curcumin can restore the impaired chloride conductance of AF508 mutant CFTR. The activity is rapid, reversible and cAMP-dependent. However, we couldn＇t reproduce the previously reported correction of the defective membrane trafficking of AF508-CFTR by curcumin. Therefore, curcumin may not be a superior lead compound for developing anti-CF drugs.Cystic fibrosis（CF） is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator（CFTR） chloride channel. The most common point mutation AF508, which leads to impaired intracellular processing and channel gating of CFTR, appears in about 90% CF patients. The natural compound curcumin was reported to correct the processing defect of AF508-CFTR and proposed as a potential therapeutic drug to cure CF. In the present study, we analyzed the effect of curcumin on AF508-CFTR and demonstrated that curcumin can restore the impaired chloride conductance of AF508 mutant CFTR. The activity is rapid, reversible and cAMP-dependent. However, we couldn＇t reproduce the previously reported correction of the defective membrane trafficking of AF508-CFTR by curcumin. Therefore, curcumin may not be a superior lead compound for developing anti-CF drugs.

关 键 词：Cystic tibrosis CFTR Mutation Natural compound Drug discovery 

分 类 号：R576[医药卫生—消化系统]