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Age-related alteration of poly(ADP-ribose) polymerase activity in different parts of the brain.

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Poly(ADP-ribose) polymerase (PARP) is a conserved enzyme involved in the regulation of DNA repair and genome stability. The role of PARP during aging is not well known. In this study PARP activity was investigated in nuclear fractions from hippocampus, cerebellum, and cerebral cortex of adult (4 months), old adult (14 months) and aged (24-27 months) rats. Concomitantly, the free radical evoked lipid peroxidation was estimated as thiobarbituric acid reactive substances (TBARS). The specific activity of PARP in adult brain was about 25, 21 and 16 pmol/mg protein per min in hippocampus, cerebellum and cerebral cortex, respectively. The enzyme activity was higher in all investigated parts of the brain of old adults. In aged animals PARP activity was lower in hippocampus by about 50%, and was unchanged in cerebral cortex and in cerebellum comparing to adult rats. The concentration of TBARS was the same in all parts of the brain and remained unchanged during aging. There is no direct correlation between PARP activity and free radical evoked lipid peroxidation during brain aging. The lowered enzyme activity in aged hippocampus may decrease DNA repair capacity which subsequently may be responsible for the higher vulnerability of hippocampal neurons to different toxic insults.
PARP   aging   brain  

Physical description
  • Polish Academy of Sciences, Medical Research Centre, Department of Cellular Signalling, A. Pawińskiego 5, 02-106 Warszawa, Poland
  • Polish Academy of Sciences, Medical Research Centre, Department of Cellular Signalling, A. Pawińskiego 5, 02-106 Warszawa, Poland
  • Polish Academy of Sciences, Medical Research Centre, Department of Neurophysiology, A. Pawińskiego 5, 02-106 Warszawa, Poland
  • Asakawa, T. & Matsushita, S. (1980) Coloring conditions of thiobarbituric acid test for detecting lipid hydroperoxides. Lipids 15, 137-140.
  • Ashok, B.T., Ahmad, J. & Ali, R. (1998) Immunochemical detection of oxidative DNA damage in cancer and aging using anti-reactive oxygen species modified DNA monoclonal antibody. Int. J. Biochem. Cell. Biol. 30, 1367-1377.
  • Ayyagari, P.U., Gerber, M., Joseph, J.A. & Crews, F.T. (1998) Uncoupling of muscarinic cholinergic phosphoinositide signals in senescent cerebral cortical and hippocampal membranes. Neurochem. Int. 32, 107-115.
  • Chaturvedi, M.M. & Kanungo, M.S. (1983) Analysis of chromatin of the brain of young and old rats by micrococcal nuclease and DNase I. Biochem. Int. 6, 357-363.
  • Chypre, C., Maniez, C. & Mandel, P. (1988) Cytoplasmic poly(ADP-ribose) polymerase associated with free messenger ribonucleoprotein particles in rat brain. J. Neurochem. 51, 561-565.
  • Cohen-Armon, M., Homburg, S., Dantzer, F., Moran, N., Visochek, L., Dekel, N., Priel, E., Schwartz, D. & Rotter, V. (1999) Activation of DNA-bound PARP: A novel target for signal transduction mechanisms. Biochimie 81, S275.
  • Cookson, M.R., Ince, P.G., Usher, P.A. & Shaw, P.J. (1999) Poly(ADP-ribose) polymerase is found in both the nucleus and cytoplasm of human CNS neurones. Brain Res. 834, 182-185.
  • Das, B.R. & Kanungo, M.S. (1986a) Involvement of ADP-ribosylation in DNA synthesis during development of rat brain. Ind. J. Biochem. Biophys. 23, 87-89.
  • Das, B.R. & Kanungo, M.S. (1986b) Developmental changes in the chromatin of the brain of the rat: Analysis by nick translation. Mol. Biol. Rep. 11, 195-197.
  • Edris, W., Burgett, B., Stine, O.C. & Filburn, C.R. (1994) Detection and quantitation by competitive PCR of an age-associated increase in a 4.8-kb deletion in rat mitochondrial DNA. Mutat. Res. 316, 69-78.
  • Grube, K. & Bürkle, 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.
  • Lu, C.Y., Lee, H.C., Fahn, H.J. & Wei, Y.H. (1999) Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin. Mutat. Res. 423, 11-21.
  • Masson, M., Niedergang, C., Schreiber, V., Muller S., Menissier-de Murcia, J. & de Murcia, G. (1998) XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol. Cell. Biol. 18, 3563-3571.
  • Mecocci, P., MacGarvey, U., Kaufman, A.E., Koontz, D., Shoffner, J.M., Wallace, D.C. & Beal, M.F. (1993) Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann. Neurol. 34, 609-616.
  • Messripour, M., Weltin, D., Rastegar, A., Ciesielski, L., Kopp, P., Chabert, M. & Mandel, P. (1994) Age-associated changes of rat brain neuronal and astroglial poly(ADP-ribose) polymerase activity. J. Neurochem. 62, 502-506.
  • Mishra, S.K. & Das, B.R. (1992) (ADP-ribosyl)ation pattern of chromosomal proteins during ageing. Cell. Mol. Biol. 38, 457-462.
  • Mishra, S.K. & Das, B.R. (1991) Poly(ADP-ribose) synthetase activity in rat testis during ageing; in: Quality Ageing, (Jaiprakash, I., ed.) pp. 47-50, Bangalore.
  • 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.
  • Quesada, P., Faraone-Mennella, M.R., Jones, R., Malanga, M. & Farina, B. (1990) ADP-ribosylation of nuclear proteins in rat ventral prostate during ageing. Biochem. Biophys. Res. Commun. 170, 900-907.
  • Realini, C.A. & Althaus, F.R. (1992) Histone shuttling by poly(ADP-ribosylation) J. Biol. Chem. 267, 18858-18865.
  • Ruscetti, T., Lehnert, B.E., Halbrook, J., Le Trong, H., Hoekstra, M.F., Chen, D.J. & Peterson, S.R. (1998) Stimulation of the DNA-dependent protein kinase by poly(ADP-ribose) polymerase. J. Biol. Chem. 273, 14461-14467.
  • Salminen, A., Helenius, M., Lahtinen, T., Korhonen, P., Tapiola, T., Soininen, H. & Solovyan, V. (1997) Down-regulation of Ku autoantigen, DNA-dependent protein kinase, and poly(ADP-ribose) polymerase during cellular senescence. Biochem. Biophys. Res. Commun. 238, 712-716.
  • Starke-Reed, P.E. (1997) Oxygen radicals and aging; in Oxygen Radicals and the Disease Process (Craig, T. & Kalyanaraman, B., ed.) pp. 65-83, Harwood Academic Publishers.
  • Strosznajder, R.P., Jęśko, H. & Strosznajder, J. (1999) Aging and amyloid beta related alteration of PARP activity and lipid peroxidation in brain and PC-12 cells in culture. J. Neurochem. 73 (Suppl.), S26B.
  • Tanigawa, Y., Kawamura, M. & Shimoyama, Y. (1976) Effect of polyamines on (ADP-ribosyl)ation of nuclear proteins from rat liver. Biochem. Biophys. Res. Commun. 76, 406-412.
  • Ueda, K., Kawaichi, M. & Hayaishi, O. (1982) Poly(ADP-ribose) synthase; in ADP-Ribosylation reactions: Biology and Medicine (Hayaishi, O & Ueda, K., eds.) pp. 117-155, Academic Press, New York.
  • Ueda, K., Inagawa, J., Kido, T., Banasik, M. & Das, B.R. (1991) Improved assays of poly(ADP- ribose) metabolizing enzymes (abstract); in: Paul Mandel International Meeting on (ADP-ribosyl)ation Reactions, Quebec, Canada (3 May-2 June) 33c.
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