Cell death in the normal developing brain, and following ionizing radiation, methyl-azoxymethanol acetate, and hypoxia-ischaemia in the rat.
Naturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia-ischaemia in the developing rat brain. Ionizing radiation-induced cell death in the brain of the young rat has morphological characteristics of apoptosis, is mediated by protein synthesis and is associated with internucleosomal DNA fragmentation. Methyl-azoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c-Jun immunore-activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c-Jun mRNA induction and de novo c-Jun protein synthesis, together with activation of c-Jun/AP-1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c-Jun-immunoreactive band at p39, which corresponds to the molecular weight of c-Jun, in control rats. However, a thick c-Jun-immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM-treated rats. A thin band immediately above the thick p62 band, suggestive of c-Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c-Jun expression is associated with apoptotic cell death in the developing central nervous system.
Ferrer
I
I
Unitat de Neuropatologia, Hospital Princeps d'Espanya, Universitat de Barcelona, Spain.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000528:radiation effects*; D002545:Brain Ischemia / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects*; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology*; D011839:Radiation, Ionizing; D051381:Rats
D008746:Methylazoxymethanol Acetate