Cyclosporine-Induced Apoptosis in Human Cardiomyocytes Through P53-Dependent Pathway

Abstract

Cyclosporine A (CsA) is the most effective and widely used immunosuppressant drug in heart, lung and kidney transplantation. However, the effect of CsA is limited by the significant toxicity. The mechanism of CsA-induced toxicity is remaining controversial. Cellular apoptosis is being suggested as a possible mediator of CsA toxicity. To date, regarding the effects of CsA on apoptosis and apoptosis-related gene regulation in cardiomyocytes remain unclear. Therefore, the current study was designed to investigate the effect of CsA on apoptosis and apoptosis-related gene p53 expression in human cardiomyocytes. We hypothesized that CsA induces apoptosis in human cardiomyocytes through p53-dependent pathway.Human cardiac atrial tissue was obtained from open-heart surgery (n=5). The cardiac tissue was minced and incubated in the special tissue culture system for 24 hours in the absence or presence of CsA (10-7 M). To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) was performed.