Nitric Oxide Activation of Poly(ADP-Ribose) Synthetase in Neurotoxicity
Abstract
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 β-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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RNS including NO are major triggers for PARP1 hyperactivation, especially in neurons.
“reactive nitrogen species (RNS) including NO stand out as major triggers for PARP1 hyperactivation, especially in neurons [659–661].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [660]
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- Authors
- Zhang, J., Dawson, V. L., Dawson, T. M., & Snyder, S. H.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Science
- Published
- 1994-02-04
- Volume
- 263
- Issue
- 5147
- Pages
- 687-689
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2005706069
- Cited by
- 1,118
- References
- 34
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 9 · 2022: 3 · 2021: 17 · 2020: 10 · 2019: 5 · 2018: 16 · 2017: 12 · 2016: 11 · 2015: 21 · 2014: 17 · 2013: 13 · 2012: 18
- FWCI
- 37.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA 00074, DA271-90-7408, DA.00266)
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- poly(ADP-ribose) polymerase, nitric oxide, neurotoxicity, ADP-ribosylation, NMDA receptor, benzamide derivatives, NAD+ depletion, ATP depletion, brain, DNA strand breaks, cell death
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Animals, Benzamides, Brain, Cell Line, Cells, Cultured, Cerebral Cortex, DNA Damage, Enzyme Activation, Humans, Neurons, Nitric Oxide, Poly(ADP-ribose) Polymerases, N-Methylaspartate, Cell Death, Rats, Sprague-Dawley, Rats
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