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首页> 外文期刊>Journal of Cellular Physiology >Matrine modulates HSC70 levels and rescues ΔF508-CFTR
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Matrine modulates HSC70 levels and rescues ΔF508-CFTR

机译：苦参碱调节HSC70水平和救援

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摘要

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent Cl - channel located in the plasma membrane, and its malfunction results in cystic fibrosis (CF), the most common lethal genetic disease in Caucasians. Most CF patients carry the deletion of Phe508 (ΔF508 mutation); this mutation prevents the delivery of the CFTR to its correct cellular location, the apical (lumen-facing) membrane of epithelial cells. Molecular chaperones play a central role in determining the fate of ΔF508-CFTR. In this report, we show that the Matrine, a quinolizidine alkaloid, downregulates the expression of the molecular chaperone HSC70 and increases the protein levels of ΔF508-CFTR in human alveolar basal epithelial cells (A549 cell line), stably transfected with a ΔF508-CFTR-expressing construct. Moreover, Matrine induced ΔF508-CFTR release from endoplasmic reticulum to cell cytosol and its localization on the cell membrane. Interestingly, downregulation of HSC70 resulted in increased levels of ΔF508-CFTR complexes with the co-chaperone BAG3 that in addition appeared to co-localize with the mutated protein on the cell surface. These results shed new light on ΔF508-CFTR interactions with proteins of the chaperones/co-chaperones system and could be useful in strategies for future medical treatments for CF.
机译：囊性纤维化跨膜电导监管机构(雌性生殖道是一个cAMP-dependent Cl -通道位于质膜,它的故障导致囊性纤维化(CF)白种人中最常见的致命的遗传性疾病。大多数CF患者携带Phe508的删除(ΔF508突变);雌性生殖道的交付正确的细胞位置,顶端(lumen-facing)膜上皮细胞。决定命运的核心作用ΔF508-CFTR。苦参碱,quinolizidine生物碱,会使分子伴侣蛋白HSC70的表达和蛋白质含量的增加ΔF508-CFTR人类肺泡基底上皮细胞(A549细胞线),稳定转染ΔF508-CFTR-expressing构造。苦参碱诱导ΔF508-CFTR释放细胞胞质和内质网定位在细胞膜上。downregulation HSC70导致增加水平的ΔF508-CFTR复合体的co-chaperone BAG3,除了出现硝唑与突变蛋白在细胞表面。ΔF508-CFTR与蛋白质的相互作用监护人/ co-chaperones系统和可能为未来的医学有用的策略CF的治疗方法。

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