Poly(ADP-Ribose) Polymerase Activity Contributes to Peroxynitrite-Induced Spinal Cord Neuronal Cell Death In Vitro
- 1 September 2004
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 21 (9), 1255-1263
- https://doi.org/10.1089/neu.2004.21.1255
Abstract
Peroxynitrite, which has been implicated in secondary neuronal damage resulting from spinal cord injury, is capable of mediating several toxic interactions including inducing DNA strand breaks and activating the nuclear enzyme, poly (ADP-ribose) polymerase (PARP). In the present study we have tested the hypothesis that peroxynitrite-induced cell death in spinal cord injury is due to activation of PARP. Initially we examined whether peroxynitrite exerts toxic effects on primary cultures of spinal cord neurons and then determined whether the spinal cord neuronal cell death triggered by peroxynitrite was associated with PARP activation. Peroxynitrite dose-dependently reduced the viability of spinal cord neurons in vitro. Furthermore, peroxynitrite exposure markedly increased the number of DNA strand breaks in primary spinal cord neurons, resulting in activation of PARP. To identify whether PARP activation plays a direct role in peroxynitrite-induced neurotoxicity we assessed the effects of the PARP inhibitors, nicotinamide, 3-aminobenzamide and 5-iodo-6-amino-1,2 benzopyrone on cell viability in spinal cord neurons exposed to peroxynitrite. The presence of the PARP inhibitors in the cultures not only inhibited peroxynitrite-induced PARP activity in spinal cord neurons but also protected the cells from the deleterious actions of peroxynitrite. Therefore, our results demonstrate that peroxynitrite exerts toxic effects on spinal cord neurons in vitro at least in part through a PARP-dependent pathway.Keywords
This publication has 48 references indexed in Scilit:
- Preliminary Study of Nicotinamide (Vitamin B3) as a Neuroprotective Agent Following Experimental Spinal Cord InjuryAcademic Emergency Medicine, 2003
- Peroxynitrite‐induced oligodendrocyte toxicity is not dependent on poly(ADP‐ribose) polymerase activationGlia, 2002
- Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing FactorScience, 2002
- Poly(ADP‐ribose) polymerase inhibition prevents both apoptotic‐like delayed neuronal death and necrosis after H2O2 injuryJournal of Neurochemistry, 2002
- Poly(ADP-ribose) polymerase inhibitors attenuate necrotic but not apoptotic neuronal death in experimental models of cerebral ischemiaCell Death & Differentiation, 2001
- Traumatic neuroprotection with inhibitors of nitric oxide and ADP-ribosylationBrain Research, 1996
- Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death.The Journal of Experimental Medicine, 1995
- Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide.JCI Insight, 1986
- Changes in the level of poly ADP-ribosylation during a cell cycleExperimental Cell Research, 1978