Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects
Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects
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DOI：
10.1126/science.1093941
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发表时间：
2004-04-23
期刊：
影响因子：
56.9
通讯作者：
Caplan, MJ
中科院分区：
文献类型：
--
作者：
Egan, ME;Pearson, M;Caplan, MJ
囊性纤维化是由编码囊性纤维化跨膜传导调节因子(CFTR)的基因突变引起的。最常见的突变是DeltaF508，它会导致错误折叠的CFTR蛋白的产生，该蛋白保留在内质网中并被降解。姜黄素是一种无毒的钙-三磷酸腺苷泵抑制剂，可以安全地应用于人体。给纯合子DeltaF508 CFTR小鼠口服姜黄素的剂量与人类对姜黄素的耐受性相当，纠正了这些动物特有的鼻部电位差缺陷。在完全敲除cftr基因的纯合子小鼠中没有观察到这些影响。姜黄素还可诱导DeltaF508 CFTR蛋白在转基因地鼠肾细胞质膜上出现功能性表达。因此，姜黄素治疗可能能够纠正与DeltaF508 CFTR纯合表达相关的缺陷。
Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator ( CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus, curcumin treatment may be able to correct defects associated with the homozygous expression of DeltaF508 CFTR.