DEGRADATION OF LAMIN B-1 PRECEDES OLIGONUCLEOSOMAL DNA FRAGMENTATION IN APOPTOTIC THYMOCYTES AND ISOLATED THYMOCYTE NUCLEI

Chromatin condensation and nuclear envelope breakdown are characterist ic features of apoptotic cell death, but the mechanisms underlying the se phenomena have not been identified. Solubilization of nuclear lamin is responsible for both events in mitosis. In this work, we report th at glucocorticoids stimulate rapid degradation of lamin B-1 that occur s before oligonucleosomal DNA fragmentation in apoptotic thymocytes. P rotease inhibitors and the Ca2+ buffering agent BAPTA-AM block lamin d egradation and DNA fragmentation, indicating that the processes are re gulated by similar or identical mechanisms. Incubation of isolated thy mocyte nuclei with Ca2+ stimulates lamin degradation before the detect ion of oligonucleosomal DNA fragments. However, in contrast to lamin d issolution during mitosis and some other forms of apoptosis, glucocort icoid-induced degradation of lamin B-1 in thymocytes is not accompanie d by dephosphorylation-mediated activation of cdc2. Our results demons trate that lamin degradation is an early feature of apoptosis in thymo cytes and suggest that chromatin condensation and breakdown of the nuc lear envelope may occur as a result of disruption of nuclear lamina ar chitecture.