APOPTOSIS-INDUCED CONCOMITANT RELEASE OF CYTOSOLIC PROTEINS AND FACTORS WHICH PREVENT CELL-DEATH

In the course of the apoptotic cell death, cells fragment into apoptot ic bodies, the elimination of which by phagocytosis is thought to avoi d the release of cytosolic constituents whose occurrence is indicative for necrotic cell death. Confluent cultures of chicken embryo fibrobl asts, however, show a different behaviour. After serum deprivation, th ey transiently released with the same time course mitogenic activity, lactate dehydrogenase and cytosolic peptidyl prolyl cis-trans isomeras es into the serum-free culture medium. The release correlated in time with a decrease of the cell number which started similar to 3 h after serum removal and ceased within similar to 10 h at about half of the i nitial cell density. Morphological features like cell shrinkage, membr ane blebbing and cell fragmentation as well as internucleosomal DNA fr agmentation indicated apoptotic cell death whereas necrotic cell death could be excluded. Conditioned medium (M-r greater than or equal to 3 0 kDa) from serum-deprived cultures of chicken embryo fibroblasts comp letely prevented chicken embryo fibroblasts to undergo apoptosis as di d phorbol 12-myristate, 13-acetate and, to similar to 60%, L-cysteine. Cycloheximide had no effect on serum deprivation-induced apoptosis. F rom the present results it can be concluded that chicken embryo fibrob lasts and possibly other cells undergoing apoptosis release cytosolic components and endogenous survival factor(s) which prevent apoptosis.