Preferences help
enabled [disable] Abstract
Number of results
2000 | 47 | 3 | 847-854
Article title

Effect of amyloid beta peptide on poly(ADP-ribose) polymerase activity in adult and aged rat hippocampus.

Title variants
Languages of publication
It is suggested that the fibrillar amyloid beta peptide (Aβ) 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 In this study the effect of neurotoxic fragment (25-35) of full length Aβ peptide on PARP activity in adult and aged rat hippocampus was investigated. In adult (4 month old) rat hippocampus the Aβ 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 Aβ 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, Aβ 25-35 did not exert any additional stimulatory effect. These results indicate that Aβ, through NO and probably other free radicals, induces activation of DNA bound PARP activity exclusively in adult but not in aged hippocampus.
Physical description
  • Department of Cellular Signalling, Medical Research Centre, Polish Academy of Sciences, A. Pawińskiego 5, 02-106 Warszawa, Poland
  • Department of Cellular Signalling, Medical Research Centre, Polish Academy of Sciences, A. Pawińskiego 5, 02-106 Warszawa, Poland
  • Department of Neurophysiology, Medical Research Centre, Polish Academy of Sciences, A. Pawińskiego 5, 02-106 Warszawa, Poland
  • 1. Pike, C.J., Walencewicz, A.J., Glabe, C.G. & Cotman, C.W. (1991) In vitro aging of β-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res. 563, 311-314.
  • 2. Pike, C.J., Ramezan-Arab, N. & Cotman, C.W. (1997) Beta-amyloid neurotoxicity in vitro: Evidence of oxidative stress but not protection by antioxidants. J. Neurochem. 69, 1601-1611.
  • 3. Mattson, M.P., Tomaselli, K.J. & Rydel, R.E. (1993) Calcium-destabilizing and neurodegenerative effects of aggregated β-amyloid peptide are attenuated by basic FGF. Brain Res. 621, 35-49.
  • 4. Busciglio, J., Lorenzo, A. & Yankner, B.A. (1992) Methodological variables in the assessment of beta amyloid neurotoxicity. Neurobiol. Aging 13, 609-612.
  • 5. Yankner, B.A., Duffy, L.K. & Kirschner, D.A. (1990) Neurotrophic and neurotoxic effects of amyloid β protein: Reversal by tachykinin neuropeptides. Science 250, 279-282.
  • 6. Strosznajder, J.B., Zambrzycka, A., Kacprzak, M.D. & Strosznajder, R.P. (1999) Amyloid β peptide 25-35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex. J. Mol. Neurosci. 12, 101-109.
  • 7. Zambrzycka, A., Strosznajder, R.P. & Strosznajder, J.B. (2000) Aggregated beta amyloid peptide 1-40 decreases Ca2+- and cholinergic receptor-mediated phosphoinositide degradation by alteration of membrane and cytosolic phospholipase C in brain cortex. Neurochem. Res. 25, 189-196.
  • 8. Mattson, M.P., Partin, J. & Begley, J.G. (1998) Amyloid-beta peptide induces apoptosis-related events in synapses and dendrites. Brain Res. 807, 167-176.
  • 9. Geula, C., Wu, C.K., Saroff, D., Lorenzo, A., Yuan, M.L. & Yankner, B.A. (1998) Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity Nature Medicine 4, 827- 831.
  • 10. Markesbery, W.R. (1997) Oxidative stress hypothesis in Alzheimer's disease. Free Radic. Biol. Med. 23, 134-147.
  • 11. Butterfield, D.A., Yatin, S.M., Varadarajan, S. & Koppal, T. (1999) Amyloid beta-peptide-associated free radical oxidative stress, neurotoxicity, and Alzheimer's disease. Methods Enzymol. 309, 746-768.
  • 12. Butterfield, D.A., Howard, B., Yatin, S., Koppal, T., Drake, J., Hensley, K., Aksenov, M., Aksenova, M., Subramaniam, R., Varadarajan, S., Harris-White, M.E., Pedigo, N.W., Jr. & Carney, J.M. (1999) Elevated oxidative stress in models of normal brain aging and Alzheimer's disease. Life Sci. 65, 1883-1892.
  • 13. Grube, K. & Burkle, A. (1992) Poly(ADP- ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span. Proc. Natl. Acad. Sci. U.S.A. 89, 11759-11763.
  • 14. Muiras, M.L., Muller, M., Schachter, F. & Burkle, A. (1998) Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians. J. Mol. Med. 76, 346-354.
  • 15. Mishra, S.K. & Das, B.R. (1992) (ADP-ribosyl)- ation pattern of chromosomal proteins during ageing. Cell. Mol. Biol. 38, 457-462.
  • 16. Chalimoniuk, M. & Strosznajder, J.B. (1998) Aging modulates nitric oxide synthesis and cGMP levels in hippocampus and cerebellum: Effects of amyloid β peptide. Mol. Chem. Neuropathol. 35, 77-95.
  • 17. Asakawa, T. & Matsushita S. (1980) Coloring conditions of thiobarbituric acid test for detecting lipid peroxides. Lipids 15, 137-140.
  • 18. Zhang, J., Pieper, A. & Snyder, S.H. (1995) Poly(ADP-ribose) synthetase activation: An early indicator of neurotoxic DNA damage. J. Neurochem. 65, 1411-1414.
  • 19. Choi, D.W. (1992) Excitotoxic cell death. J. Neurobiol. 23, 1261-1276.
  • 20. Rothman, S.M. & Olney, J.W. (1986) Glutamate and the patophysiology of hypoxic- ischemic brain damage. Ann. Neurol. 19, 105-111.
  • 21. Chalimoniuk, M. & Strosznajder, J. (1998) NMDA receptor-dependent nitric oxide and cGMP synthesis in brain hemispheres and cerebellum during reperfusion after transient forebrain ischemia in gerbils: Effect of 7-nitroindazole. J. Neurosci. Res. 54, 681-690.
  • 22. Dawson, V.L., Dawson, T.M., London, E.D., Bredt, D.S. & Snyder, S.H. (1991) Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc. Natl. Acad. Sci. U.S.A. 88, 6368-6371.
  • 23. Dawson, D.A. (1994) Nitric oxide and focal cerebral ischemia: Multiplicity of actions and diverse outcome. Cerebrovasc. Brain Metab. Rev. 6, 299-324.
  • 24. Beckamn, J.S. (1994) Peroxynitrite vs hydroxyl radical: The role of NO in superoxide-mediated cerebral injury. Ann. N.Y. Acad. Sci. 738, 69-75.
  • 25. Chan, P.H. (1996) Role of oxidants in ischemic brain damage. Stroke 27, 1124-1129.
  • 26. Love, S., Barber, R. & Wilcock, G.K. (1999) Neuronal accumulation of poly(ADP-ribose) after brain ischemia. Neurophatol. Appl. Neurobiol. 25, 98-103.
  • 27. Zhang, J., Dawson, V.L., Dawson, T.M. & Snyder, S.H. (1994) Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263, 687-689.
  • 28. Le, W.D., Colom, L.V., Xie, W.J., Smith, R.G., Alexianu, M. & Appel, S.H. (1994) Cell death induced by β-amyloid 1-40 in MES 23.5 hybrid clone: The role of nitric oxide and NMDA- gated channel activation leading to apoptosis. Brain Res. 686, 49-60.
  • 29. Mattson, M.P., Cheng, B., Davis, D., Bryant, K., Lieberburg, I. & Rydel, R.E. (1992) β-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J. Neurosci. 12, 376-389.
  • 30. Strosznajder, J., Jęśko, H. & Strosznajder, R.P. (2000) Age-related alteration of poly(ADP-ribose) polymerase activity in different parts of the brain. Acta Biochim. Polon. 47, 331-337.
  • 31. Pike, C.J., Burdick, D., Walencewicz, A.J., Glabe, C.G. & Cotman, C.W. (1993) Neurodegeneration induced by beta-amyloid peptides in vitro: The role of peptide assembly state. J. Neurosci. 13, 1676-1687.
  • 32. Pike, C.J., Overman, M.J. & Cotman, C.W. (1995) Amino-terminal deletions enhance aggregation of beta-amyloid peptides in vitro. J. Biol. Chem. 270, 23895-23898.
  • 33. Roher, A.E., Ball, M.J., Bhave, S.V. & Wakade, A.R. (1991) β-Amyloid from Alzheimer disease brains inhibits sprouting and survival of sympathetic neurons. Biochem. Biophys. Res. Commun. 174, 572-579.
  • 34. Emre, M., Geula, C., Ransil, B.J. & Mesulam, M.M. (1992) The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected β-amyloid in the rat brain. Neurobiol. Aging 13, 553-559.
  • 35. Frautschy, S.A., Baird, A. & Cole, G.M. (1991) Effects of injected Alzheimer's β-amyloid cores in rat brain. Proc. Natl. Acad. Sci. U.S.A. 88, 8362-8366.
  • 36. Kowall, N.W., Beal, M.B., Busciglio, J., Duffy, L.K. & Yankner, B.A. (1991) An in vivo model for the neurodegenerative effects of β amyloid and protection by substance P. Proc. Natl. Acad. Sci U.S.A. 88, 7247-7251.
  • 37. Games, D., Khan, K.M., Soriano, F.G., Keim, P.S., Davis, D.L., Bryant, K. & Lieberburg, I. (1992) Lack of Alzheimer pathology after β-amyloid protein injections in rat brain. Neurobiol. Aging 13, 569-576.
  • 38. Podlisny, M.B., Stephenson, D.T., Frosch, M.P., Tolan, D.R., Lieberburg, I., Clemens, J.A. & Selkoe, D.J. (1993) Microinjection of synthetic amyloid β-protein in monkey cerebral cortex fails to produce acute neurotoxicity. Am. J. Pathol. 142, 17-24.
  • 39. Gray, C.W. & Patel, A.J. (1995) Neurodegeneration mediated by glutamate and beta-amyloid peptide: A comparison and possible interaction. Brain Res. 691, 169-179.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.