During the differentiation and maturation of thymocytes, autoreactive cells ar known to be deleted in the thymus, but the mechanism of cell death has not been elucidated. To elucidate the mechanisms involved in mouse thymocyte apoptosis induced
by
dibutyryl cyclic adenosine monophosphate(dhcAMP) or prostaglandin E2(PGE20, thymocytes were treated with stimulators or stimulators plus inhibitors of macromolecules for various times in accordance with the purpose of this research. Stimulation
of
thymocytes with dbcAMP(50μM) or PGE2(1μM) for 6hrs resulted in 60-70% fragmentation of DNA into 180-200bp multiples. DbcAMP-or PGE2-induced DNA fragmentation was inhibited by inhibitors of RNA, protein synthesis, or endonuclease. PGE2-or
dbcAMP-induced DNA fragmentation was blocked by epidermal growth factor(EGF0, but was not blocked by PKC inhibitor. However, the cytosolic calcium concentration increased slightly when stimulated by dbcAMP or PGE2 in thymocyte. Data obtained with
cAMP
analogs and PGE2, which are known to act synergistically to stimulate protein kinase A (PKA) suggested that the latter directly mediated endonuclease activation. The thymocytes whch showed the highest susceptibilities for the in vitro exposures
to
PGE2
or dbcAMP belonged to the subpopulation of CD4+ CD8+ immature cells.
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