Author + information
- Lin Zhang,
- Jiamei Liu,
- Juan Zhang,
- Hua Wang,
- Zhiyong Zhang,
- Xin Wang,
- Jin Chen,
- Hakon Hakonarson,
- Aihua Hu,
- Lin Xu and
- Dongyan Hou
Previously, we reported that a missense mutation (C722G) in the M2-muscarinic acetylcholine receptor (CHRM2) geneis associated with familial dilated cardiomyopathy (DCM). However, the exact molecular mechanisms by the fundamental changes involved in the CHRM2 signaling pathways in patients with the C722G mutation are still not clear.
In this study, we generated CHRM2 and CHRM2-C722G lentiviral vector and applied to infect the CHO cells. Then we performed proteomic analyses by label free shotgun strategy and analyzed the most changed proteins by the STRING 9.0 software-Known and Predicted Protein-Protein Interactions.
A total of 102 proteins with at least 2-fold change in the cells transfected with CHRM2-C722G were identified, 42 proteins were upregulated, whereas 57 proteins were down-regulated. These altered proteins belong to three broad functional categories: (i) metabolic [e.g. Ubiquitin-like modifier-activating enzyme 1, Cytosolic acyl coenzyme A thioester hydrolase, Malate dehydrogenase and Arginyl-tRNA synthetase]; (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 and Ras GTPase-activating protein-binding protein2). Interestingly, the marked differences in the expression of selected eight proteins (change>4.0-fold), including heat shock protein 70, Malate dehydrogenase, Sodium/potassium -transporting ATPase subunit alpha-1, Ubiquitin-like modifier-activating enzyme 1,et al were connected with many proteins related to apoptosis and immune/inflammatory response such as: FOS, BAX, MYC, TP53 and IL6, which are involved in the pathology of congestive heart failure.
We have carried out a full-scale screening of the proteomics research under condition of C722G mutation in the CHRM2 gene related to familial DCM and profiled the eight proteins which may be critical in cardiac dysfunction for future mapping.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: New Insights into Heart Failure Pathophysiology
Abstract Category: 16. Heart Failure: Basic
Presentation Number: 1222-298
- 2013 American College of Cardiology Foundation