ArticleScientific reports2017
PDI regulates seizure activity via NMDA receptor redox in rats.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Distinct Roles of NMDA and AMPA Receptors in the Pathogenesis of Hyperbaric Oxygen-Induced Seizures.Biomedicines · 2026Article
- The Role of Disulfide Bonds in the GluN1 Subunit in the Early Trafficking and Functional Properties of GluN1/GluN2 and GluN1/GluN3 NMDA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Hydrogen Sulfide (HInternational journal of molecular sciences · 2025Review
- Protein disulfide isomerase integrates toll-like receptor 4 and P2X7 receptor signaling pathways during lipopolysaccharide-induced neuroinflammation.Scientific reports · 2025Article
- The role of molecular chaperones in the mechanisms of epileptogenesis.Cell stress & chaperones · 2023Review
- PDI augments kainic acid-induced seizure activity and neuronal death by inhibiting PP2A-GluA2-PICK1-mediated AMPA receptor internalization in the mouse hippocampus.Scientific reports · 2023Article
- CDDO-Me Abrogates Aberrant Mitochondrial Elongation in Clasmatodendritic Degeneration by Regulating NF-κB-PDI-Mediated S-Nitrosylation of DRP1.International journal of molecular sciences · 2023Article
- Protein disulfide isomerase modulation of TRPV1 controls heat hyperalgesia in chronic pain.Cell reports · 2022Article
- The Unfolded Protein Response in the Human Infant Brain and Dysregulation Seen in Sudden Infant Death Syndrome (SIDS).Molecular neurobiology · 2021Article
- Protein disulfide isomerase-mediated S-nitrosylation facilitates surface expression of P2X7 receptor following status epilepticus.Journal of neuroinflammation · 2021Article
- Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy.Frontiers in molecular neuroscience · 2021Review
- Effects of Heat Shock Protein 90 Inhibition In the Lungs.Medicine in drug discovery · 2020Article
- PDI-Mediated Reduction of Disulfide Bond on PSD95 Increases Spontaneous Seizure Activity by Regulating NR2A-PSD95 Interaction in Epileptic Rats Independent ofInternational journal of molecular sciences · 2020Article
- TMT-Based Proteomic Analysis of Plasma from Children with Rolandic Epilepsy.Disease markers · 2020Article
- Unmasking GluN1/GluN3A excitatory glycine NMDA receptors.Nature communications · 2018Article
- PDI-mediated S-nitrosylation of DRP1 facilitates DRP1-S616 phosphorylation and mitochondrial fission in CA1 neurons.Cell death & disease · 2018Article
- PDI Knockdown Inhibits Seizure Activity in Acute Seizure and Chronic Epilepsy Rat Models viaFrontiers in cellular neuroscience · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Redox modulation of cysteine residues is one of the post-translational modifications of N-methyl-D-aspartate receptor (NMDAR). Protein disulfide isomerases (PDI), an endoplasmic reticulum (ER) chaperone, plays a crucial role in catalyzing disulfide bond formation, reduction, and isomerization. In the present study, we found that PDI bound to NMDAR in the normal hippocampus, and that this binding was increased in chronic epileptic rats. In vitro thiol reductase assay revealed that PDI increased the amount of thiols on full-length recombinant NR1 protein. PDI siRNA, 5-5'-dithio-bis(2-nitrobenzoic acid) (DTNB), bacitracin and PDI antibody reduced seizure susceptibility in response to pilocarpine. In addition, PDI knockdown effectively ameliorated spontaneous seizure activity in chronic epileptic rats. Anticonvulsive effects of PDI siRNA were correlated to the reduction of the amount of free- and nitrosothiols on NMDAR, accompanied by the inhibition of PDI activity. However, PDI knockdown did not lead to alteration in basal neurotransmission or ER stress under physiological condition. These findings provide mechanistic insight into sulfhydration of disulfide bonds on NMDAR by PDI, and suggest that PDI may represent a target of potential therapeutics for epilepsy, which avoids a possible side effect on physiological receptor functionality.
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