28S ribosome degradation in lymphoid cell apoptosis: evidence for caspase and Bcl-2-dependent and -independent pathways

Apoptosis, a physiological form of cell death, is characterized by the acti vation of a program that kills cells and recycles their constituents. We ha ve used thymoma cell lines to examine the role of Bcl-2 and caspases in rib osomal destruction during apoptosis, Glucocorticoid and calcium ionophore ( A23187)-induced apoptosis of S49 Neo cells resulted in both 28S rRNA and DN A degradation. Interestingly, anisomycin, a potent protein synthesis inhibi tor, also induced 28S rRNA and DNA fragmentation suggesting that the respon sible nucleases are present in the viable cells and become activated during apoptosis, The anti apoptotic protein, Bcl-2, inhibited both glucocorticoi d and anisomycin induced DNA and 28S rRNA degradation but could not protect against A23187 induced nucleic acid degradation. We next examined the role of caspase activation in the generation of 28S rRNA degradation through th e use of ZVAD, a general caspase inhibitor. Under conditions where ZVAD sub stantially decreased 28S rRNA degradation induced by glucocorticoid or anis omycin, no decrease was observed when A23187 was used to induce apoptosis, Surprisingly, RNA degradation, like DNA degradation, occurs exclusively in shrunken lymphocytes but not those with normal cell volume despite equivale nt exposure of the cells to the apoptotic signals. Together, these findings indicate the ribosome is a specific target for death effecters during apop tosis and that a caspase/Bcl-2-independent pathway exists to activate its d estruction.