EARLY GENE SIGNALING-DEPENDENT AND SIGNALING-INDEPENDENT INDUCTION OFAPOPTOSIS IN RAMOS HUMAN B-CELLS CAN BE INHIBITED BY OVER-EXPRESSION OF BCL-2

We have previously shown that calcium ionophore-induced apoptosis of R amos human B cells is preceded by the induced expression of early resp onse genes, implying a requirement for new gene expression in this mod e of programmed cell death. We have found in the present studies that inhibitors of macromolecular synthesis, cycloheximide and actinomycin D, are also potent inducers of apoptosis in the same Ramos cell model. These drugs trigger apoptosis through apparently early gene signallin g-independent pathways. Although different mechanisms for induction of apoptosis exist in Ramos cells, enforced over-expression of Bcl-2 pro tects cells from apoptosis induced in response to different agents, de monstrating that Bcl-2 blocks a final common pathway for programmed ce ll death hi the Ramos cell model. (C) 1995 Academic Press, Inc.