Department of Prosthodontics and the Dental Research Center, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Expert Rev Proteomics. 2014 Jun;11(3):395-404. doi: 10.1586/14789450.2014.896742. Epub 2014 Mar 31.
Cerebral cavernous malformations (CCM) are vascular anomalies caused by mutations in genes encoding KRIT1, OSM and PDCD10 proteins causing hemorrhagic stroke. We examine proteomic change of loss of CCM gene expression. Using human umbilical vein endothelial cells, label-free differential protein expression analysis with multidimensional liquid chromatography/tandem mass spectrometry was applied to three CCM protein knockdown cell lines and two control cell lines: ProteomeXchange identifier PXD000362. Principle component and cluster analyses were used to examine the differentially expressed proteins associated with CCM. The results from the five cell lines revealed 290 and 192 differentially expressed proteins (p < 0.005 and p < 0.001, respectively). Most commonly affected proteins were cytoskeleton-associated proteins, in particular myosin-9. Canonical genetic pathway analysis suggests that CCM may be a result of defective cell-cell interaction through dysregulation of cytoskeletal associated proteins.
The work explores signaling pathways that may elucidate early detection and novel therapy for CCM.
脑静脉血管畸形（CCM）是由 KRIT1、OSM 和 PDCD10 蛋白基因突变引起的血管畸形，可导致出血性中风。我们研究了 CCM 基因表达缺失的蛋白质组变化。使用人脐静脉内皮细胞，通过多维液相色谱/串联质谱进行无标记差异蛋白质表达分析，应用于三个 CCM 蛋白敲低细胞系和两个对照细胞系：ProteomeXchange 标识符 PXD000362。主成分和聚类分析用于研究与 CCM 相关的差异表达蛋白。这五个细胞系的结果显示 290 和 192 种差异表达蛋白（p<0.005 和 p<0.001）。受影响最常见的蛋白质是细胞骨架相关蛋白质，特别是肌球蛋白-9。经典遗传途径分析表明，CCM 可能是由于细胞-细胞相互作用的缺陷，通过细胞骨架相关蛋白的失调而导致的。
这项工作探索了可能阐明 CCM 的早期检测和新疗法的信号通路。
