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Science 4 February 1994:
Vol. 263. no. 5147, pp. 687 - 689
DOI: 10.1126/science.8080500
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Articles

Science, Vol 263, Issue 5147, 687-689
Copyright © 1994 by American Association for the Advancement of Science

articles

Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity

J Zhang, VL Dawson, TM Dawson, and SH Snyder

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Poly(adenosine 5'-diphosphoribose) synthetase (PARS) is a nuclear enzyme which, when activated by DNA strand breaks, adds up to 100 adenosine 5'-diphosphoribose (ADP-ribose) units to nuclear proteins such as histones and PARS itself. This activation can lead to cell death through depletion of beta-nicotinamide adenine dinucleotide (the source of ADP-ribose) and adenosine triphosphate. Nitric oxide (NO) stimulated ADP-ribosylation of PARS in rat brain. Benzamide and other derivatives, which inhibit PARS, blocked N-methyl-D-aspartate- and NO-mediated neurotoxicity with relative potencies paralleling their ability to inhibit PARS. Thus, NO appeared to elicit neurotoxicity by activating PARS.


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Stroke 29, 2404-2411
   Abstract »    Full Text »    PDF »
Poly(ADP-Ribose) Synthetase Activation Mediates Mitochondrial Injury During Oxidant-Induced Cell Death.
L. Virag, A. L. Salzman, and C. Szabo (1998)
J. Immunol. 161, 3753-3759
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Inducible Nitric Oxide: An Autoregulatory Feedback Inhibitor of Vascular Inflammation.
H.-B. Peng, M. Spiecker, and J. K. Liao (1998)
J. Immunol. 161, 1970-1976
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Genetic Disruption of Poly (ADP-Ribose) Synthetase Inhibits the Expression of P-Selectin and Intercellular Adhesion Molecule-1 in Myocardial Ischemia/Reperfusion Injury.
B. Zingarelli, A. L. Salzman, and C. Szabo (1998)
Circ. Res. 83, 85-94
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Effects of Nitric Oxide on Adenylyl Cyclase Stimulation in N18TG2 Neuroblastoma Cells.
Y.-P. Tao, L. Najafi, S. Shipley, A. Howlett, and C. Klein (1998)
J. Pharmacol. Exp. Ther. 286, 298-304
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Inhibition of Poly(ADP-Ribose) Polymerase : Reduction of Ischemic Injury and Attenuation of N-Methyl-D-Aspartate–Induced Neurotransmitter Dysregulation • Editorial Comment: Reduction of Ischemic Injury and Attenuation of N-Methyl-D-Aspartate–Induced Neurotransmitter Dysregulation.
E. H. Lo, P. Bosque-Hamilton, W. Meng, and N. Panahian (1998)
Stroke 29, 830-836
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Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets.
C. L. Schleien, J. W. Kuluz, and B. Gelman (1998)
Am J Physiol Heart Circ Physiol 274, H1378-H1385
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Manganese Superoxide Dismutase Protects nNOS Neurons from NMDA and Nitric Oxide-Mediated Neurotoxicity.
M. Gonzalez-Zulueta, L. M. Ensz, G. Mukhina, R. M. Lebovitz, R. M. Zwacka, J. F. Engelhardt, L. W. Oberley, V. L. Dawson, and T. M. Dawson (1998)
J. Neurosci. 18, 2040-2055
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Resistance of Neuronal Nitric Oxide Synthase-Deficient Mice to Methamphetamine-Induced Dopaminergic Neurotoxicity.
Y. Itzhak, C. Gandia, P. L. Huang, and S. F. Ali (1998)
J. Pharmacol. Exp. Ther. 284, 1040-1047
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Nitric oxide inhibits Na+ absorption across cultured alveolar type II monolayers.
Y. Guo, M. D. Duvall, J. P. Crow, and S. Matalon (1998)
Am J Physiol Lung Cell Mol Physiol 274, L369-L377
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Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis.
D. C. Hooper, S. Spitsin, R. B. Kean, J. M. Champion, G. M. Dickson, I. Chaudhry, and H. Koprowski (1998)
PNAS 95, 675-680
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Response of Postmitotic Neurons to X-Irradiation: Implications for the Role of DNA Damage in Neuronal Apoptosis.
G. T. Gobbel, M. Bellinzona, A. R. Vogt, N. Gupta, J. R. Fike, and P. H. Chan (1998)
J. Neurosci. 18, 147-155
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Neuroprotective Effects of Creatine and Cyclocreatine in Animal Models of Huntington's Disease.
R. T. Matthews, L. Yang, B. G. Jenkins, R. J. Ferrante, B. R. Rosen, R. Kaddurah-Daouk, and M. F. Beal (1998)
J. Neurosci. 18, 156-163
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Neuronal Nitric Oxide Synthase Inhibition Reduces Neuronal Apoptosis After Hypothermic Circulatory Arrest.
E. E. Tseng, M. V. Brock, M. S. Lange, M. E. Blue, J. C. Troncoso, C. C. Kwon, C. J. Lowenstein, M. V. Johnston, and W. A. Baumgartner (1997)
Ann. Thorac. Surg. 64, 1639-1647
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Delayed Reduction of Ischemic Brain Injury and Neurological Deficits in Mice Lacking the Inducible Nitric Oxide Synthase Gene.
C. Iadecola, F. Zhang, R. Casey, M. Nagayama, and M. E. Ross (1997)
J. Neurosci. 17, 9157-9164
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Topical Review: Glutamate in Neurologic Diseases.
P. Bittigau and C. Ikonomidou (1997)
J Child Neurol 12, 471-485
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Growth and viability of macrophages continuously stimulated to produce nitric oxide.
J. C. Zhuang and G. N. Wogan (1997)
PNAS 94, 11875-11880
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Inhibition of poly (ADP-ribose) Synthetase Attenuates Neutrophil Recruitment and Exerts Antiinflammatory Effects.
C. Szabo, L. H.K. Lim, S. Cuzzocrea, S. J. Getting, B. Zingarelli, R. J. Flower, A. L. Salzman, and M. Perretti (1997)
J. Exp. Med. 186, 1041-1049
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Nitric Oxide Synthases and Cardiac Muscle : Autocrine and Paracrine Influences.
J.-L. Balligand and P. J. Cannon (1997)
Arterioscler Thromb Vasc Biol 17, 1846-1858
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Parathyroid Hormone–Related Protein Upregulates Interleukin-1ß–Induced Nitric Oxide Synthesis.
B. Jiang, S. Morimoto, J. Yang, K. Fukuo, A. Hirotani, S. Kitano, and T. Ogihara (1997)
Hypertension 30, 922-927
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