title: Proteomics screen to reveal molecular changes mediated by C722G missense mutation in CHRM2 gene.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Heart Failure Center, Department of Cardiology, Capital Medical University, Chao-Yang Hospital, Beijing, China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Hou
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiamei
authors.initials: J
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Rongrui
authors.initials: R
authors.lastname: Zhao
authors.forename: Aihua
authors.initials: A
authors.lastname: Hu
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D006801:Humans; D016086:Lentivirus; D020125:Mutation, Missense; D020543:Proteome / Q000096:biosynthesis* / Q000235:genetics; D043585:Receptor, Muscarinic M2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: C487078:CHRM2 protein, human; D020543:Proteome; D043585:Receptor, Muscarinic M2
keywords: Cytoskeleton; Immune/inflammatory response; Metabolism; Shotgun proteomics