Curcumin enhances cystic fibrosis transmembrane regulator expression by down-regulating calreticulin
Curcumin enhances cystic fibrosis transmembrane regulator expression by down-regulating calreticulin
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DOI：
10.1016/j.bbrc.2006.12.036
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发表时间：
2007-02-09
影响因子：
3.1
通讯作者：
Kai, Hirofumi
中科院分区：
文献类型：
--
作者：
Harada, Kazutsune;Okiyoneda, Tsukasa;Kai, Hirofumi
据报道，姜黄素可以纠正囊性纤维化跨膜调节基因Delta F508突变引起的囊性纤维化，但其作用机制尚不清楚。我们最近证实，内质网伴侣钙网蛋白(CRT)负向调节CFTR细胞表面的表达和活性。因此，我们旨在确定CRT是否介导了姜黄素对CFTR的影响。我们发现，姜黄素处理的中国仓鼠卵巢细胞抑制CRT的表达，增加野生型CFTR的表达，但不影响Delta F508 CFTR的表达。然而，我们发现，尽管姜黄素不能增强Delta F508 CFTR的表达，但它增强了26℃孵育诱导的Delta F508 CFTR的功能。用siRNA在低温下敲除CRT也有类似的效果。我们的研究结果表明，姜黄素对CFTR表达的积极作用是通过下调CFTR的负调控因子CRT实现的。(C)2006 Elsevier Inc.保留所有权利。
Curcumin has been reported to correct cystic fibrosis caused by the Delta F508 mutation of the cystic fibrosis transmembrane regulator (CFTR) but its mechanistic action remains unclear. We have recently demonstrated that the ER chaperone calreticulin (CRT) negatively regulates the CFTR cell surface expression and activity. Thus, we aimed at determining whether CRT mediates the effect of curcumin on CFTR. We show here that the treatment with curcumin of Chinese hamster ovary cells suppressed CRT expression and increased wildtype CFTR but did not affect Delta F508 CFTR expression. However, we determined that although curcumin did not augment Delta F508 CFTR expression, it enhanced the functional competence of Delta F508 CFTR induced by 26 degrees C incubation. Knock down of CRT by siRNA at low-temperature had a similar effect. Our findings suggest that the positive effect of curcumin on CFTR expression is mediated through the down-regulation of CRT, a negative regulator of CFTR. (c) 2006 Elsevier Inc. All rights reserved.