NATURALLY-OCCURRING (PROGRAMMED) AND RADIATION-INDUCED APOPTOSIS ARE ASSOCIATED WITH SELECTIVE C-JUN EXPRESSION IN THE DEVELOPING RAT-BRAIN

Expression of the different members of transcription factors Fos and J un was examined in the developing rat brain. Constitutive expression o f c-Fos, Fos-related antigens, Jun B and Jun D, as revealed with immun ohistochemistry, is higher and more widely distributed in the developi ng rat brain than in the adult. Selective strong c-Jun expression is o bserved in the cytoplasm and nuclei of apoptotic cells during the whol e process of naturally occurring (programmed) cell death. Cells expres sing strong c-Jun immunoreactivity are undetermined cells, neurons and astrocytes. Selective c-Jun expression is also observed following ion izing radiation in rats aged 3 days. Induction of c-jun mRNA, as revea led with in situ hybridization, occurs between 5 and 15 min following gamma-irradiation. Strong c-jun protein expression appears at 2 h, pea ks at 6 h and decreases thereafter to reach normal levels 48 h after g amma-ray exposure. Strong c-Jun protein expression is coincidental wit h endonuclease activation, as revealed with the method of in situ labe lling of nuclear DNA fragmentation, and is restricted to apoptotic cel ls. Cycloheximide injection at the time of irradiation blocks c-Jun ex pression, indicating that c-jun immunoreactivity is attributable to de novo protein synthesis. These observations demonstrate in vivo select ive strong c-Jun expression associated with programmed cell death and ionizing radiation-induced apoptosis in the developing rat brain.