Effect of amyloid beta peptide on poly(ADP-ribose) polymerase activity in adult and aged rat hippocampus.
It is suggested that the fibrillar amyloid beta peptide (A beta) in brain plays a direct role in neurodegeneration in Alzheimer's disease, probably through activation of reactive oxygen species formation. Free radicals and numerous neurotoxins elicit DNA damage that subsequently activates poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30). In this study the effect of neurotoxic fragment (25-35) of full length A beta peptide on PARP activity in adult and aged rat hippocampus was investigated. In adult (4 month old) rat hippocampus the A beta 25-35 peptide significantly enhanced PARP activity by about 80% but had no effect on PARP activity in cerebral cortex and in hippocampus from aged (24-27 month old) rats. The effect of A beta peptide was reduced by half by the nitric oxide synthase inhibitor N-nitro-L-arginine. Stimulation of glutamate receptor(s) itself enhanced PARP activity by about 80% in adult hippocampus. However, A beta 25-35 did not exert any additional stimulatory effect. These results indicate that A beta, through NO and probably other free radicals, induces activation of DNA bound PARP activity exclusively in adult but not in aged hippocampus.
Strosznajder
J B
JB
Department of Cellular Signalling, Medical Research Centre, Polish Academy of Sciences, Warszawa. joannas@cmdik.pan.pl
Jeśko
H
H
Strosznajder
R P
RP
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D005609:Free Radicals / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D016202:N-Methylaspartate; D011065:Poly(ADP-ribose) Polymerases