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The Journal of Neuroscience, August 10, 2005, 25(32):7420-7428; doi:10.1523/JNEUROSCI.0333-05.2005

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Cellular/Molecular
PolyADP-Ribosylation Is Involved in Neurotrophic Activity

Leonid Visochek,1 Ruth A. Steingart,1,2 Ina Vulih-Shultzman,1,2 Rodica Klein,1 Esther Priel,1,3 Illana Gozes,1,2 and Malka Cohen-Armon1

1The Neufeld Cardiac Research Institute and 2Department of Clinical Biochemistry, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel, and 3Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University, Beer Sheva 84105, Israel

PolyADP-ribosylation is a transient posttranslational modification of proteins, mainly catalyzed by poly(ADP-ribose)polymerase-1 (PARP-1). This highly conserved nuclear protein is activated rapidly in response to DNA nick formation and promotes a fast DNA repair. Here, we examine a possible association between polyADP-ribosylation and the activity of neurotrophins and neuroprotective peptides taking part in life-or-death decisions in mammalian neurons. The presented results indicate an alternative mode of PARP-1 activation in the absence of DNA damage by neurotrophin-induced signaling mechanisms. PARP-1 was activated in rat cerebral cortical neurons briefly exposed to NGF-related nerve growth factors and to the neuroprotective peptides NAP (the peptide NAPVSIPQ, derived from the activity-dependent neuroprotective protein ADNP) and ADNF-9 (the peptide SALLRSIPA, derived from the activity-dependent neurotrophic factor ADNF) In addition, polyADP-ribosylation was involved in the neurotrophic activity of NGF-induced and NAP-induced neurite outgrowth in differentiating pheochromocytoma 12 cells as well as in the neuroprotective activity of NAP in neurons treated with the Alzheimer's disease neurotoxin {beta}-amyloid. A fast loosening of the highly condensed chromatin structure by polyADP-ribosylation of histone H1, which renders DNA accessible to transcription and repair, may underlie the role of polyADP-ribosylation in neurotrophic activity.

Key words: PARP-1; polyADP-ribosylation; Ca2+ signaling; nerve growth factors; neuroprotective peptides; NAP; ADNF-9

Received Jan 24, 2005; revised May 31, 2005; accepted June 30, 2005.






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