Modulation of thymocyte apoptosis by isoproterenol and prostaglandin E2.

Isoproterenol and prostaglandin E2 increased cAMP levels in mouse thymocytes transiently, but failed to induce significant internucleosomal DNA fragmentation in thymocytes with a 24-hr incubation. However, these substances showed synergistic interaction with forskolin in the accumulation of cAMP and DNA fragmentation. The addition of 12-O-tetradecanoyl 13-acetate, an activator of protein kinase C, with isoproterenol or particularly with prostaglandin E2 enhanced DNA fragmentation. These results indicate that an increase in cAMP mediated by isoproterenol or prostaglandin receptor is involved in thymocyte apoptosis through internucleosomal DNA fragmentation in concert with a second signal, the activation of protein kinase C.