Programmed cell death in heterokaryons. A study of the transfer of apoptosis between nuclei.
Thymocytes undergoing apoptosis induced by dexamethasone showed nuclear refractivity changes under Nomarski optics that correlated precisely with internucleosomal DNA degradation and was prevented by cycloheximide. When heterokaryons between thymocytes and 9L or NIH3T3 cells were examined, 99.75% of the nuclei in heterokaryons followed the original and distinct fate characteristic of the parental cells. Thymocyte nuclei proceeded to undergo apoptotic cell death, whereas the 9L and NIH3T3 nuclei in the heterokaryons did not show the morphologic changes of apoptosis or any DNA cleavage on gels, and remained viable and mitotic. Cycloheximide prevented the induction of apoptosis in thymocyte nuclei in the heterokaryons. An excess of up to seven thymocyte nuclei undergoing programmed cell death in a heterokaryon did not detectably damage the 9L nucleus, and an excess of six 9L nuclei did not protect the thymocyte nucleus from apoptosis. The proposed model stating that programmed cell death results from de novo synthesis of death-causing gene products is difficult to reconcile with these findings. A cell-type-specific activity, present in thymocyte nuclei before induction of apoptosis with corticosteroids and unable to diffuse between nuclei, appears to be responsible for DNA fragmentation. These results also show that nuclear disintegration is the trigger of thymocyte death and not a consequence of cell death due to another mechanism.
Dipasquale
B
B
Biochemistry Section, SNB-NINDS, National Institutes of Health, Bethesda, MD 20892-0010.
Youle
R J
RJ
D000818:Animals; D017209:Apoptosis; D002450:Cell Communication; D016923:Cell Death; D002459:Cell Fusion; D002467:Cell Nucleus / Q000648:ultrastructure*; D002843:Chromatin / Q000648:ultrastructure; D003600:Cytosol / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008853:Microscopy / Q000379:methods; D013950:Thymus Gland / Q000166:cytology* / Q000648:ultrastructure
D002843:Chromatin