PolyADP-ribosylation is involved in neurotrophic activity.

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 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.

• Authors: Leonid Visochek, Ruth A Steingart, Ina Vulih-Shultzman, Rodica Klein, Esther Priel, Illana Gozes, Malka Cohen-Armon
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 25 Issue 32 Pg. 7420-8 (Aug 10 2005) ISSN: 1529-2401 [Electronic] United States
• PMID: 16093393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amyloid beta-Peptides
• Histones
• Nerve Growth Factors
• Neuroprotective Agents
• Oligopeptides
• activity-dependent neurotrophic factor
• Poly Adenosine Diphosphate Ribose
• Parp1 protein, rat
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases
• davunetide

Topics

• Amyloid beta-Peptides (pharmacology)
• Animals
• Cells, Cultured
• Cerebral Cortex (cytology, drug effects, metabolism)
• Enzyme Activation
• Histones (metabolism)
• Nerve Growth Factors (pharmacology, physiology)
• Neurites (drug effects, physiology)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oligopeptides (pharmacology)
• PC12 Cells
• Poly (ADP-Ribose) Polymerase-1
• Poly Adenosine Diphosphate Ribose (metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• Rats
• Signal Transduction (physiology)