Protective Effect of PKC Affecting Gliotoxin-induced Cytotoxicity in Rat Smooth Muscle Cells / 대한해부학회지

ABSTRACT

Aspergillus funigatus and other pathogenic fungi synthesize a toxic epidithi-odiopiperzine (ETP) metabolite, namely gliotoxin. Gliotoxin commonly react with sulfhydryl groups, and then, forms hydrogen peroxide. These fungal toxins induce apoptotic cell death in various cells. Apoptosis induced by gliotoxin need calcium. Effect of calcium preconditioning was not reported in gliotoxin-induced apoptosis. To examine the effect of protein kinase C (PKC) and calcium which was regulate caspase-3, PKC and calcium preconditioning before gliotoxin treatment, apoptotic agents such as bcl-2 family, caspase-3 and DNA fragmentation in A7r5 cell line from rat smooth muscle cell were studied. These results showed that gliotoxin induces the expression of bad of bcl-2 family, caspase-3 activation and DNA fragmentation in A7r5 cells. Gliotoxin treatment followed by calcium and PKC preconditioning suppress the Bad of bcl-2 family, and inhibited caspase-3 activation, respectively. These results suggest that PKC and calcium preconditioning protect the gliotoxin-induced apoptosis, through the protection of pro-apoptotic bcl-2 family in A7r5 cells.