Post-Translational Modification Networks of Contractile and Cellular Stress Response Proteins in Bladder Ischemia.

Post-Translational Modification Networks of Contractile and Cellular Stress Response Proteins in Bladder Ischemia.
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膀胱缺血中收缩和细胞应激反应蛋白的翻译后修饰网络。

DOI:
10.3390/cells10051031
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发表时间:
2021-04-27
期刊:
影响因子:
6
通讯作者:
Azadzoi KM
Azadzoi KM
中科院分区:
生物学2区
文献类型:
--
作者:
Yang JH;Choi HP;Yang A;Azad R;Chen F;Liu Z;Azadzoi KM

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缺血性膀胱功能障碍的分子机制,特别是在蛋白质和蛋白质修饰水平和下游途径,在很大程度上仍然未知。在这里,我们描述了缺血和正常膀胱组织中的蛋白质序列变异的比较,通过测量的编码氨基酸和实际残基的质量差异的蛋白质组。检测到大量非零δ质量(11,056),跨越1295个蛋白质残基。聚类分析确定了12个显著失调的δ质量簇,涉及膀胱缺血中30个上调(R2 > 0.5,比率> 2,p < 0.05)和33个下调(R2 > 0.5,比率<-2,p < 0.05)蛋白。这些蛋白质残基具有与标准编码氨基酸不同的质量权重,表明在膀胱缺血中形成非编码氨基酸(ncAA)残基。这些缺血相关的δ-质量包含蛋白质的途径,基因本体论,和蛋白质-蛋白质相互作用网络分析表明,缺血引起了几个氨基酸的变化,潜在的翻译后修饰,在膀胱收缩蛋白和应激反应分子。ncAA的蓄积可能是平滑肌功能障碍的新生物标志物,具有膀胱功能障碍的诊断潜力。我们的数据表明,全球蛋白质修饰的系统评估可能是至关重要的缺血性疾病的特点一般和缺血性膀胱功能障碍的病理机制。
Molecular mechanisms underlying bladder dysfunction in ischemia, particularly at the protein and protein modification levels and downstream pathways, remain largely unknown. Here we describe a comparison of protein sequence variations in the ischemic and normal bladder tissues by measuring the mass differences of the coding amino acids and actual residues crossing the proteome. A large number of nonzero delta masses (11,056) were detected, spanning over 1295 protein residues. Clustering analysis identified 12 delta mass clusters that were significantly dysregulated, involving 30 upregulated (R2 > 0.5, ratio > 2, p < 0.05) and 33 downregulated (R2 > 0.5, ratio < −2, p < 0.05) proteins in bladder ischemia. These protein residues had different mass weights from those of the standard coding amino acids, suggesting the formation of non-coded amino acid (ncAA) residues in bladder ischemia. Pathway, gene ontology, and protein–protein interaction network analyses of these ischemia-associated delta-mass containing proteins indicated that ischemia provoked several amino acid variations, potentially post-translational modifications, in the contractile proteins and stress response molecules in the bladder. Accumulation of ncAAs may be a novel biomarker of smooth muscle dysfunction, with diagnostic potential for bladder dysfunction. Our data suggest that systematic assessment of global protein modifications may be crucial to the characterization of ischemic conditions in general and the pathomechanism of bladder dysfunction in ischemia.
DOI: 10.1002/path.4659
发表时间: 2016-01
期刊: The Journal of pathology
影响因子: --
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