PolyADP-ribosylation is involved in neurotrophic activity

Leonid Visochek, Ruth A. Steingart, Ina Vulih-Shultzman, Rodica Klein, Esther Priel, Illana Gozes, Malka Cohen-Armon

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)7420-7428
Number of pages9
JournalJournal of Neuroscience
Volume25
Issue number32
DOIs
StatePublished - 10 Aug 2005

Keywords

  • ADNF-9
  • Ca signaling
  • NAP
  • Nerve growth factors
  • Neuroprotective peptides
  • PARP-1
  • PolyADP-ribosylation

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