02 May 2003 : Case report
Peroxynitrite-induced toxicity in spinal cord neurons is dependent on poly(ADP-ribose) polymerase activation
G. Scott, D. Hooper, C. SzaboMed Sci Monit 2003; 9(1): 59-0 :: ID: 15198
Abstract
Spinal cord trauma initiates a series of sequential events that lead to neuronal cell death. While the precise mechanisms responsible for this secondary damage remain undefined, several studies have suggested that free radicals contribute to the neurodestructive processes of spinal cord injury [1]. Moreover, peroxynitrite, a highly reactive molecule generated when nitric oxide and superoxide combine, has recently been proposed to induce secondary neuronal damage resulting from spinal cord injury [2–5]. Peroxynitrite can mediate several destructive interactions, including activation of poly(ADP-ribose) polymerase (PARP). In the present study we have examined whether peroxynitrite exerts toxic effects on primary cultures of spinal cord neurons via activation of PARP. Peroxynitrite dose-dependently reduced the viability of spinal cord neurons in culture and induced cell death. Furthermore, exposure to peroxynitrite markedly increased DNA strand breaks in spinal cord neurons resulting in activation of PARP. To determine whether PARP activation plays a role in peroxynitrite-induced neurotoxicity we assessed the effects of various PARP inhibitors on cell viability and death in spinal cord neurons exposed to peroxynitrite. The presence of PARP inhibitors in the cultures protected spinal cord neurons from the deleterious actions of peroxynitrite. Therefore, our results demonstrate that peroxynitrite exerts cytotoxic effects on spinal cord neurons in vitro through a PARP-dependent pathway. References: 1.Anderson DK, Hall ED: Pathophysiology of spinal cord trauma. Ann Emerg Med, 1993; 22: 987-992 2.Scott GS, Jakeman LB, Stokes BT, Szabó C: Peroxynitrite production and activation of poly(adenosine diphosphate-ribose) synthetase in spinal cord injury. Ann Neurol, 1999; 45: 120-124 3.Liu D, Ling X, Wen J, Liu J: The role of reactive nitrogen species in secondary spinal cord injury: Formation of nitric oxide, peroxynitrite and nitrated protein. J Neurochem, 2000; 75: 2144-2154 4.Xu J, Kim G-M, Chen S, Yan P et al: iNOS and nitrotyrosine expression after spinal cord injury. J Neurotrauma, 2001; 18: 523-532 5.Bao F, Liu D: Peroxynitrite generated in the rat spinal cord induces neuron death and neurological deficits. Neuroscience, 2002; 115: 839-849
Keywords: spinal cord injury, peroxynitrite, PARP
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
26 Feb 2024 : Clinical Research
Predictive Value of Combined HbA1c and Neutrophil-to-Lymphocyte Ratio for Diabetic Peripheral Neuropathy in...Med Sci Monit In Press; DOI: 10.12659/MSM.942509
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952