Elevated expression of C3G protein in the peri-infarct myocardium of rats

Abstract

BackgroundThe integrin β1 subunit and its downstream molecules such as integrin-linked kinase (ILK) and focal adhesion kinase (FAK) are indispensable to the inhibition of postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure. As a component of the integrin pathway, C3G (Crk SH3-domain-binding guanine nucleotide exchange factor) protein may also participate in postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure.Material/MethodsExperimental myocardial infarction (MI) and sham-operation (sham) models were set up in Sprague-Dawley rats. C3G protein expression in the myocardium in the sham group and in the non-infarcted myocardium of the peri-infarct zones in the MI group was examined by Western blot.ResultsThe C3G protein expression in the myocardium was 0.22±0.06, n=8 in the post-sham 24-hour group; 0.29±0.10, n=8 in the post-MI 24-hour group; 0.22±0.07, n=8 in the post-sham 12-week group; and 0.56±0.14, n=8 in the post-MI 12-week group. The C3G protein expression in the myocardium in the post-MI 12-week group was significantly elevated compared to that in the post-sham 12-week group (p=0.0002), in the post-sham 24-hour group (p=0.0002), and in the post-MI 24-hour group (p=0.0006).ConclusionsC3G protein expression exhibits in the myocardium of rats. Furthermore, C3G protein expression is significantly elevated in the non-infarcted myocardium of the peri-infarct zones. The elevated C3G protein expression could participate in postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure.

Pro-survival effect of Dock180 overexpression on rat-derived H9C2 cardiomyocytes

“…Survival inhibition and apoptosis in cardiomyocytes are among the major causes of the pathogenesis of many cardiovascular diseases such as diabetic and ischemic ventricular enlarged cardiomyopathy, and systolic heart failure [9–11]. A novel therapy targeting the integrin pathway could be developed to benefit patients with cardiovascular diseases [12] because of its anti-apoptotic and pro-survival effects on the cardiomyocytes [6].…”

C3G overexpression promotes the survival of rat‐derived H9C2 cardiomyocytes by p‐ERK1/2

“…C3G binds with N‐terminal SH3 domain of its upstream adaptors such as Crk and CrkL following stimulation by signals through integrin, and subsequently activates GTPases such as Rap1, Ras and Rac1. C3G exhibits in the peri‐infarct myocardium (Wang et al, ), and regulates apoptosis, cytoskeleton polymerisation and cell proliferation in non‐cardiomyocytes (Radha et al, ). However, little is known about its role in the apoptosis, F‐actin cytoskeleton polymerisation and cell proliferation and survival in the cardiomyocytes.…”

Knockdown of CkrL by shRNA deteriorates hypoxia/reoxygenation‐induced H9C2 cardiomyocyte apoptosis and survival inhibition Via Bax and downregulation of P‐Erk1/2

“…[1][2][3] Increased apoptosis and cell survival inhibition in cardiomyocytes are the major causes of cardiomyocyte loss, ischemia/ reperfusion or H/R-induced myocardial injuries, postinfarction ventricular enlarged cardiomyopathy and systolic heart failure. 1,4,5 Targeting integrin pathway is a novel therapy measure for the previously mentioned cardiovascular diseases 6 because of its effects of cytoskeleton polymerisation and anti-apoptosis and prosurvival on the cardiomyocytes. 7,8 Integrin pathway links extracellular matrix substances to actin cytoskeleton in cardiomyocytes, and senses mechanical stretch, and translates it into intracellular biochemical signalling.…”