An Yan, Gang Li, Xu Zhang, Bingbao Zhu, Hua Linghu
Med Sci Monit Basic Res 2013; 19:12-19
Background: Integrin â1 subunit and its downstream molecule, focal adhesion kinase (FAK), have been demonstrated to be indispensible to the promotion of cell proliferation and survival and anti-apoptosis in cardiomyocytes via activation of their downstream pro-survival signaling molecule, AKT. As a component of the integrin pathway, Dock180 (dedicator of cytokinesis 1) protein is also thought to be involved in the promotion of cell proliferation and survival and anti-apoptosis in the H9C2 cardiomyocytes.
Material/Methods: Rat-derived H9C2 cardiomyocytes were transfected with pCXN2-flag-hDock180, a human Dock180 overexpression eukaryotic recombinant plasmid. The rat and human Dock180 mRNA and protein expression, apoptosis and cell proliferation and survival were analyzed in the H9C2 cardiomyocytes treated with either hypoxia/reoxygenation (H/R) or not, respectively.
Results: Human Dock180 mRNA overexpression could significantly increase the Dock180 protein expression in the H9C2 cardiomyocytes, no matter whether treated with H/R or not. Dock180 overexpression could promote the cell proliferation and survival and anti-apoptosis, and relieve the cell proliferative and survival inhibition and apoptosis induced by H/R in the H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule AKT.
Conclusions: Dock180 could act as a pro-survival molecule in H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule, AKT.
Keywords: Proto-Oncogene Proteins c-akt - metabolism, Phosphorylation, Myocytes, Cardiac - metabolism, Integrins - metabolism, Cytoskeleton - metabolism, Cell Survival, Cell Proliferation, Cell Line, Apoptosis - genetics, Animals, Actins - metabolism, RNA, Messenger - metabolism, Rats, Signal Transduction, rac GTP-Binding Proteins - metabolism