Expression of cell death-associated proteins in neuronal apoptosis associated with pontosubicular neuron necrosis

Expression of apoptosis-associated proteins p53, bcl-2, bax, and caspase-3/ CPP32, activation of caspase-3, and modification of proteins via poly(ADP-r ibosyl)ation was studied in pontosubicular neuron necrosis (PSN), a form of perinatal brain damage revealing the morphological hallmarks of neuronal a poptosis, Immunoreactivity for p53 was completely absent. The majority of c ells stained with the bax and procaspase-3 antibodies did not show morpholo gical signs of apoptosis, In contrast, an antibody against activated caspas e-3 almost exclusively stained cells with apoptotic morphology, Poly(ADP-ri bosyl)ated proteins were only rarely detected in cells with apoptotic morph ology. The expression patterns of bax, procaspase-3, bcl-2, and p53 in PSN were similar to that found in age-matched control brains, However, activate d caspase-3 and poly-ADP-ribosylated proteins were exclusively found in apo ptotic cells. These data indicate that detection of active caspase-3 is a r eliable marker for apoptosis in formalin-fixed human tissue, and that neuro nal apoptosis in pontosubicular neuron necrosis is accompanied by a pronoun ced activation of caspase-3.