ArticleProceedings of the National Academy of Sciences of the United States of America2013
S-nitrosylated SHP-2 contributes to NMDA receptor-mediated excitotoxicity in acute ischemic stroke.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- The Bright and Dark Sides of Nitric Oxide in Neurodegenerative Diseases.Journal of personalized medicine · 2026Review
- Multifaceted role of nitric oxide in vascular dementia.Medical gas research · 2025Review
- S-nitrosylation of paired-related homeobox 1 promotes cardiac remodeling following myocardial infarction.Redox biology · 2025Article
- Review
- Targeting Shp2 as a therapeutic strategy for neurodegenerative diseases.Translational psychiatry · 2025Review
- Mechanisms of synergistic suppression of ALK-positive lung cancer cell growth by the combination of ALK and SHP2 inhibitors.Scientific reports · 2023Article
- Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis.Nature communications · 2023Article
- Nitrosative stress in Parkinson's disease.NPJ Parkinson's disease · 2022Review
- Regional Differences in S-Nitrosylation in the Cortex, Striatum, and Hippocampus of Juvenile Male Mice.Journal of molecular neuroscience : MN · 2021Article
- Chronically altered NMDAR signaling in epilepsy mediates comorbid depression.Acta neuropathologica communications · 2021Article
- N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.Advances in experimental medicine and biology · 2021Article
- Post-Translational S-Nitrosylation of Proteins in Regulating Cardiac Oxidative Stress.Antioxidants (Basel, Switzerland) · 2020Review
- Coordination between Calcium/Calmodulin-Dependent Protein Kinase II and Neuronal Nitric Oxide Synthase in Neurons.International journal of molecular sciences · 2020Review
- Systems biology reveals reprogramming of the S-nitroso-proteome in the cortical and striatal regions of mice during aging process.Scientific reports · 2020Article
- Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function.Molecular psychiatry · 2020Article
- S-nitrosylation of E3 ubiquitin-protein ligase RNF213 alters non-canonical Wnt/Ca+2 signaling in the P301S mouse model of tauopathy.Translational psychiatry · 2019Article
- Mitochondrial Dysfunction in Neural Injury.Frontiers in neuroscience · 2019Review
- S-Nitrosylation of Divalent Metal Transporter 1 Enhances Iron Uptake to Mediate Loss of Dopaminergic Neurons and Motoric Deficit.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis.Brain : a journal of neurology · 2018Article
- S-Nitrosylation Regulates Cell Survival and Death in the Central Nervous System.Neurochemical research · 2018Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Overproduction of nitric oxide (NO) can cause neuronal damage, contributing to the pathogenesis of several neurodegenerative diseases and stroke (i.e., focal cerebral ischemia). NO can mediate neurotoxic effects at least in part via protein S-nitrosylation, a reaction that covalently attaches NO to a cysteine thiol (or thiolate anion) to form an S-nitrosothiol. Recently, the tyrosine phosphatase Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) and its downstream pathways have emerged as important mediators of cell survival. Here we report that in neurons and brain tissue NO can S-nitrosylate SHP-2 at its active site cysteine, forming S-nitrosylated SHP-2 (SNO-SHP-2). We found that NMDA exposure in vitro and transient focal cerebral ischemia in vivo resulted in increased levels of SNO-SHP-2. S-Nitrosylation of SHP-2 inhibited its phosphatase activity, blocking downstream activation of the neuroprotective physiological ERK1/2 pathway, thus increasing susceptibility to NMDA receptor-mediated excitotoxicity. These findings suggest that formation of SNO-SHP-2 represents a key chemical reaction contributing to excitotoxic damage in stroke and potentially other neurological disorders.
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