首页> 外文期刊>American Journal of Physiology >Induction of HSP70 promotes DeltaF508 CFTR trafficking.
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Induction of HSP70 promotes DeltaF508 CFTR trafficking.

机译:HSP70的诱导促进DeltaF508 CFTR的贩运。

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摘要

The DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) is a temperature-sensitive trafficking mutant that is detected as an immature 160-kDa form (band B) in gel electrophoresis. The goal of this study was to test the hypothesis that HSP70, a member of the 70-kDa heat shock protein family, promotes DeltaF508 CFTR processing to the mature 180-kDa form (band C). Both pharmacological and genetic techniques were used to induce HSP70. IB3-1 cells were treated with sodium 4-phenylbutyrate (4PBA) to promote maturation of DeltaF508 CFTR to band C. A dose-dependent increase in band C and total cellular HSP70 was observed. Under these conditions, HSP70-CFTR complexes were increased and 70-kDa heat shock cognate protein-CFTR complexes were decreased. Increased DeltaF508 CFTR maturation was also seen after transfection with an HSP70 expression plasmid and exposure to glutamine, an inducer of HSP70. With immunofluorescence techniques, the increased appearance of CFTR band C correlated with CFTR distribution beyond the perinuclear regions. These data suggest that induction of HSP70 promotes DeltaF508 CFTR maturation and trafficking.
机译:DeltaF508囊性纤维化跨膜电导调节剂(CFTR)是温度敏感的运输突变体,在凝胶电泳中被检测为不成熟的160 kDa形式(B带)。这项研究的目的是检验以下假设:HSP70是70 kDa热激蛋白家族的成员,可将DeltaF508 CFTR加工促进为成熟的180 kDa形式(C带)。药理和遗传技术均用于诱导HSP70。用4-苯基丁酸钠(4PBA)处理IB3-1细胞,以促进DeltaF508 CFTR成熟到C带。观察到C带和总细胞HSP70呈剂量依赖性增加。在这些条件下,HSP70-CFTR复合物增加,而70-kDa热激相关蛋白-CFTR复合物减少。用HSP70表达质粒转染并暴露于HSP70的诱导剂谷氨酰胺后,还可以看到DeltaF508 CFTR成熟度的增加。使用免疫荧光技术,CFTR带C的增加外观与CFTR分布超出核周区域相关。这些数据表明HSP70的诱导促进DeltaF508 CFTR成熟和贩运。

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