Proteomics screen to reveal molecular changes mediated by C722G missense mutation in CHRM2 gene

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• 作者：Dongyan Hou ; Ying Chen ; Jiamei Liu ; Lin Xu ; Zhiyong Zhang ; Juan Zhang ; Hua Wang ; Xin Wang ; Jin Chen ; Rongrui Zhao ; Aihua Hu ; Hakon Hakonarson ; Lin Zhang ; Yan Shen
• 关键词：Shotgun proteomics ; Metabolism ; Cytoskeleton ; Immune/inflammatory response
• 刊名：Journal of Proteomics
• 出版年：2013
• 出版时间：26 August, 2013
• 年：2013
• 卷：89
• 期：Complete
• 页码：39-50
• 全文大小：1640 K

文摘

Previously, we reported a missense mutation (C722G) in the M2-muscarinic acetylcholine receptor (CHRM2) gene associated with familial dilated cardiomyopathy. However, the exact molecular mechanisms by the related protein changes of CHRM2-C722G mutation induced are still unclear. CHRM2 and CHRM2-C722G lentiviral vector was infected to CHO cells. Proteomic analysis by label-free shotgun strategy and the STRING 9.0 software were performed. A total of 102 proteins with at least 2-fold change in the CHRM2-C722G group were identified, 42 proteins were up-regulated, whereas 57 were down-regulated. These altered proteins belong to three broad functional categories: (i) metabolic (e.g. Cytosolic acyl coenzyme A thioester hydrolase, Malate dehydrogenase); (ii) cytoskeletal (e.g. Actin-related protein, Myosin light polypeptide 6 and Alpha-actinin-1) and (iii) stress response (e.g. heat shock protein 70, Ras-related protein Rab-10). Interestingly, the marked differences in the expression of selected eight proteins (change > 4.0-fold), were connected with many proteins related to apoptosis and immune/inflammatory response such as: FOS, BAX, MYC, TP53 and IL6. This novel study demonstrated for the first time a full-scale screening of the proteomics research by CHRM2-C722G mutation and profiled 102 changed proteins, of which, eight might be critical in cardiac dysfunction for future mapping.

Significance

It was a full-scale screening of the proteomics research by CHRM2-C722G mutation. These proteins might serve as valuable biomarkers that could predict the presence of a precursor field. These proteins might serve to further explore the pathophysiological mechanisms in familial DCM patients with C176W mutation.