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Proteomic analysis of nasal cells from cystic fibrosis patients and non-cystic fibrosis control individuals: Search for novel biomarkers of cystic fibrosis lung disease.

机译:囊性纤维化患者和非囊性纤维化控制个体鼻细胞的蛋白质组学分析:寻找囊性纤维化肺病的新生物标记。

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摘要

Potential biological markers for cystic fibrosis (CF) lung disease were identified by comparative proteomics profiling of nasal cells from deletion of phenylalanine residue 508 (F508del)-homozygous CF patients and non-CF controls. From the non-CF 2-DE gels, 65 spots were identified by MS, and a reference 2-DE map was thus established. The majority of those correspond to ubiquitously expressed proteins. Consistent with the epithelial origin of this tissue, some of the identified proteins are epithelial markers (e.g. cytokeratins, palate lung and nasal epithelium clone protein (PLUNC), and squamous cell carcinoma antigen 1). Comparison of this protein profile with the one similarly obtained for CF nasal cells revealed a set of differentially expressed proteins. These included proteins related to chronic inflammation and some others involved in oxidative stress injury. Alterations were also observed in the levels of cytoskeleton proteins, being probably implicated with cytoskeleton organization changes described to occur in CF-airways. Lower levels were found for some mitochondrial proteins suggesting an altered mitochondrial metabolism in CF. Differential expression was also found for two more enzymes that have not been previously associated to CF. Further studies will clarify the involvement of such proteins in CF pathophysiology and whether they are targets for CF therapy.
机译:通过从缺失苯丙氨酸残基508(F508del)-纯合CF患者和非CF对照的鼻细胞进行比较蛋白质组学分析,确定了囊性纤维化(CF)肺疾病的潜在生物学标记。从非CF 2-DE凝胶中,通过MS鉴定出65个斑点,从而建立了参考2-DE图。这些中的大多数对应于普遍表达的蛋白质。与该组织的上皮起源一致,某些鉴定出的蛋白质是上皮标记物(例如,细胞角蛋白,pa肺和鼻上皮克隆蛋白质(PLUNC)以及鳞状细胞癌抗原1)。将该蛋白质谱与从CF鼻细胞获得的蛋白质谱进行比较,发现了一组差异表达的蛋白质。其中包括与慢性炎症有关的蛋白质,以及与氧化应激损伤有关的其他蛋白质。还观察到细胞骨架蛋白水平的变化,可能与描述在CF气道中发生的细胞骨架组织变化有关。发现某些线粒体蛋白水平较低,表明CF中的线粒体代谢发生了变化。还发现了另外两种以前与CF不相关的酶的差异表达。进一步的研究将阐明此类蛋白在CF病理生理中的作用,以及它们是否是CF治疗的靶标。

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