Role of cytoskeletal proteins in cerebral cavernous malformation signaling pathways: a proteomic analysis.

Autor: Baxter SS; David H. Murdock Research Institute, North Carolina Research Campus, Kannapolis, NC 28081, USA., Dibble CF, Byrd WC, Carlson J, Mack CR, Saldarriaga I, Bencharit S
Jazyk: angličtina
Zdroj: Molecular bioSystems [Mol Biosyst] 2014 Jul; Vol. 10 (7), pp. 1881-9.
DOI: 10.1039/c3mb70199a
Abstrakt: Three genetic mutations were found to cause cerebral cavernous malformation (CCM), a vascular anomaly predisposing affected individuals to hemorrhagic stroke. These CCM proteins function together as a protein complex in the cell. Loss of expression of each CCM gene results in loss of in vitro endothelial tube formation. Label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) was applied to explore the proteomic profile for loss of each CCM gene expression in mouse endothelial stem cells (MEES) compared to mock shRNA and no shRNA control cell-lines. Differentially expressed proteins were identified (p < 0.05). 120 proteins were differentially expressed among the cell-lines. Principal component analysis and cluster analysis show the effects of individual knockdown. In all knockdown cell-lines, altered expression of cytoskeletal proteins is the most common. While all CCM mutations result in similar pathology, different CCM mutations have their own distinct pathogenesis in cell signaling.
Databáze: MEDLINE