Effect Of Apoptosis Repressor With Caspase Recruitment Domain On The Gene Expression Of Insulin-induced Cardiomvocvte Hypertrophy C-myc In Broiler

Broiler ascites syndrome, a serious metabolic disease inducing high morbidity and mortality rate, has caused serious losses in broiler production worldwide. One prominent symptom of broiler ascites syndrome is right ventricular hypertrophy caused by the self-hypertrophy of myocardial cells rather than an increase in the number of myocardial cells. Apoptosis repressor with caspase recruitment domain (ARC) is primarily and highly expressed in the heart and brain. Originally, ARC was believed to be just caspase-2and caspase-8interacting with each other. ARC can prevent cell apoptosis and hypertrophy by preserving mitochondrial function. The proto-oncogene c-myc has a pivotal role in growth control, hypertrophy, and apoptosis. Its abnormal expression is associated with several naturally occurring neoplasms. c-myc is expressed in almost all proliferating normal cells, where its expression strictly depends on mitogenic stimuli c-myc, which is critical for cellular growth in several cell types, is induced by virtually all interventions that lead to cardiac hypertrophy, either in cultured cells or in the intact myocardium. Hence, it is a likely candidate for direct mediation of hypertrophic cardiac growth Transient overexpression of c-myc in cultured neonatal cardiac myocytes results in increased DNA synthesis and protein content.Accordingly, this study aimed to determine the effect of ARC on the expression of c-myc in insulin-induced cardiomyocyte hypertrophy in a chick embryo cardiomyocyte culture.This study aimed to observe the effect of apoptosis repressor with caspase recruitment domain (ARC) on the gene expression of insulin-induced cardiomyocyte hypertrophy c-myc in a chick embryo cardiomyocyte culture. Chick embryo cardiomyocytes were acquired from9-to11-day-old chick myocardial tissue, and then treated with collagenase II digestion and induced with hypertrophy by insulin. The diameter and surface area of the cardiomyocytes were measured as hypertrophy indicators. Recombinant PEGFP-N1/ARC plasmid was obtained and transfected into the chick embryo cardiomyocytes. The expression of the proto-oncogene c-myc mRNA and protein in the cardiomyocytes was detected by real time PCR and ELIS A, respectively. Treatment with insulin (10-7mol/L) lasted for48h. After treatment, the cardiomyocyte diameter (17.66±1.346μm) significantly increased (P<0.05) compared with the control group (15.57±1.803μm). The cardiomyocyte surface area (283.8±62.8μm2) significantly increased (P<0.05) compared with the control group (231.0±148.3μm2). The expression of both c-myc mRNA and protein increased (P<0.05) after insulin addition. After the transformation of PEGFP-N1/ARC, the action of insulin was affected, the c-myc mRNA and protein expression levels decreased (P<0.05). ARC can inhibit insulin-induced cardiomyocyte hypertrophy, which may relate to the inhibition of expression of the proto-oncogene c-myc.Ca2+is the most common intracellular signal transduction component with an important role in inducing the expression of proto-oncogene and cardiac hypertrophy. As a calcium-binding protein, ARC maintains the balance of intracellular Ca2+. ARC protein can connect with Ca2+through its C-terminus, and then block the intracellular Ca2+increase caused by ATP stimulation, thereby inhibiting cell hypertrophy and apoptosis. Therefore, the inhibition of cardiomyocyte hypertrophy by ARC protein may be related to the inhibition of expression of proto-oncogenes in myocardial cells or to the inhibition of intracellular Ca2+concentration. The specific mechanisms of action require further study.