PolyADP-ribosylation is involved in neurotrophic activity.
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.
Visochek
Leonid
L
The Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Steingart
Ruth A
RA
Vulih-Shultzman
Ina
I
Klein
Rodica
R
Priel
Esther
E
Gozes
Illana
I
Cohen-Armon
Malka
M
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D016716:PC12 Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
D016229:Amyloid beta-Peptides; D006657:Histones; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; D011064:Poly Adenosine Diphosphate Ribose; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C425904:davunetide