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-ribosyl)ation was studied in pontosubicular neuron necrosis (PSN), a form of perinatal brain damage revealing the morphological hallmarks of neuronal apoptosis. Immunoreactivity for p53 was completely absent. The majority of cells stained with the bax and procaspase-3 antibodies did not show morphological signs of apoptosis. In contrast, an antibody against activated caspase-3 almost exclusively stained cells with apoptotic morphology. Poly(ADP-ribosyl)ated proteins were only rarely detected in cells with apoptotic morphology. The expression patterns of bax, procaspase-3, bcl-2, and p53 in PSN were similar to that found in age-matched control brains. However, activated caspase-3 and poly-ADP-ribosylated proteins were exclusively found in apoptotic cells. These data indicate that detection of active caspase-3 is a reliable marker for apoptosis in formalin-fixed human tissue, and that neuronal apoptosis in pontosubicular neuron necrosis is accompanied by a pronounced activation of caspase-3.
Stadelman
C
C
Department of Neuropathology, Charité, Humboldt-Universität, Berlin, Germany.
Mews
I
I
Srinivasan
A
A
Deckwerth
T L
TL
Lassmann
H
H
Brück
W
W
D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000378:metabolism / Q000473:pathology; D005311:Fetal Hypoxia / Q000378:metabolism / Q000473:pathology*; D005404:Fixatives / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D020869:Gene Expression Profiling; D019254:Genes, bcl-2; D016158:Genes, p53; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011064:Poly Adenosine Diphosphate Ribose / Q000032:analysis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011149:Pons / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D015415:Biomarkers; D004792:Enzyme Precursors; D005404:Fixatives; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D005557:Formaldehyde; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases