The role of S‐nitrosylation of kainate‐type of ionotropic glutamate receptor 2 in epilepsy induced by kainic acid

Wang, Linxiao; Liu, Yanyan; Lu, Renjie; Dong, Guoying; Xia, Chen; Yun, Wenwei; Zhou, Xianju

doi:10.1111/jnc.14266

Cited by 9 publications

(6 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The detailed mechanism for GRIK2 gene‐related epilepsy incidence was not well known. Recent data showed GRIK2 could undergo post‐translational modifications in terms of S‐nitrosylation (SNO) and affect the signaling pathway of cell death in cerebral ischemia‐reperfusion. SNO‐GRIK2 plays an important role in neuronal injury of epileptic rats by forming GRIK2‐PSD95‐nNOS signaling module in a cytoplasmic calcium‐dependent way, suggesting a potential therapeutic target site for epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children

Xiong

Wang

et al. 2019

Acta Neurol Scand

View full text Add to dashboard Cite

Aims The association of single nucleotide polymorphisms (SNPs) of glutamate receptor 2 (GRIK2) gene, as well as gene‐gene interaction with the risk of early‐onset epilepsy susceptibility, was studied in Chinese children. Methods Generalized multi‐factor dimension reduction (GMDR) is used to identify the optimal linkage between interaction among four SNPs and early‐onset epilepsy susceptibility. Logistic regression was performed to assess association between four SNPs within GRIK2 gene and the risk of epilepsy. Results The results show that the risk of epilepsy in the rs4840200‐T allele carriers was significantly higher than CC (CT/TT vs CC), adjusted OR (95% CI) = 1.74 (1.31‐2.20), and the carrier of rs3213607‐A allele was also higher than CC (CG/GG vs CC) with adjusted OR (95% CI) = 1.61 (1.23‐2.10). We did not detect significant association between rs9390754 and rs2235076 within GRIK2 gene and epilepsy risk. In the GMDR analysis for the gene/gene interaction (2‐4 locus models), we found a significant two‐locus model (P = 0.001) involving rs4840200 and rs9390754. The cross‐validation consistency was 10/10, and the prediction error was 0.632. Participants with rs4840200‐CT/TT and rs9390754‐GA/AA genotype within GRIK2 gene have the highest epilepsy risk, compared to participants with rs4840200‐CC and rs9390754‐GG genotype within GRIK2 gene, OR (95% CI) = 2.42 (1.78‐3.11), after covariates adjustment for age and gender. Conclusions Both rs4840200‐T and rs3213607‐A, and the interactions between rs4840200 and rs9390754 are related to the increased risk of epilepsy risk.

show abstract

Section: Discussionmentioning

confidence: 99%

Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children

Xiong

Wang

et al. 2019

Acta Neurol Scand

View full text Add to dashboard Cite

show abstract

“…A goat polyclonal anti‐nNOS antibody (ab1376; Abcam, RRID AB_300614) was raised against the synthetic peptide (ESKKDTDEVFSS) corresponding to amino acids 1423–1434 of Human NOS1. An immunoblotting analysis of this antibody labeled a band near 160‐kDa in the rat hippocampus (Wang et al, 2018). This antibody has also been used for immunohistochemical analyses of the rat NG and dorsal root ganglion (Masliukov et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

Morphology of P2X3‐immunoreactive basket‐like afferent nerve endings surrounding serosal ganglia and close relationship with vesicular nucleotide transporter‐immunoreactive nerve fibers in the rat gastric antrum

Hirakawa

Yokoyama

Yamamoto

et al. 2021

J of Comparative Neurology

View full text Add to dashboard Cite

We previously reported P2X3 purinoceptor (P2X3)‐expressing vagal afferent nerve endings with large web‐like structures in the subserosal tissue of the antral lesser curvature, suggesting that these nerve endings were one of the vagal mechanoreceptors. The present study investigated the morphological relationship between P2X3‐immunoreactive nerve endings and serosal ganglia in the rat gastric antrum by immunohistochemistry of whole‐mount preparations using confocal scanning laser microscopy. P2X3‐immunoreactive basket‐like subserosal nerve endings with new morphology were distributed laterally to the gastric sling muscles in the distal antrum of the lesser curvature. Parent axons ramified into numerous nerve fibers with pleomorphic flattened structures to form basket‐like nerve endings, and the parent axons were originated from large net‐like structures of vagal afferent nerve endings. Basket‐like nerve endings wrapped around the whole serosal ganglia, which were characterized by neurofilament 200 kDa‐immunoreactive neurons with or without neuronal nitric oxide synthase immunoreactivity and S100B‐immunoreactive glial cells. Furthermore, basket‐like nerve endings were localized in close apposition to dopamine beta‐hydroxylase‐immunoreactive sympathetic nerve fibers immunoreactive for vesicular nucleotide transporter. These results suggest that P2X3‐immunoreactive basket‐like nerve endings associated with serosal ganglia are the specialized ending structures of vagal subserosal mechanoreceptors in order to increase the sensitivity during antral peristalsis, and are activated by ATP from sympathetic nerve fibers and/or serosal ganglia for the regulation of mechanoreceptor function.

show abstract

“…The S-nitrosylation of GluK2 accelerates the generation of the SNO-GluK2/PSD95/nNOS complex, which causes neuronal damage. Pharmacological inhibition of S-nitrosylation ameliorates epilepsy-induced cell death [ 55 ]. During epilepsy-mediated cell death, membrane targeting of the P2X7receptor plays a crucial role.…”

Section: Human Disease and Nitrosationmentioning

confidence: 99%

“…Two S-nitrothiols in the P2X7 receptor form a secondary SS bridge, which maturates the P2X7 receptor structure and localizes in the membrane. Neighboring microglia and astrocytes recognize the P2X7 receptor with the SS bridge, and neuroinflammation processes are generated [ 55 ].…”

Section: Human Disease and Nitrosationmentioning

confidence: 99%

Nitrosative Stress and Human Disease: Therapeutic Potential of Denitrosylation

Yoon

Eom

Kang

2021

IJMS

View full text Add to dashboard Cite

Proteins dynamically contribute towards maintaining cellular homeostasis. Posttranslational modification regulates the function of target proteins through their immediate activation, sudden inhibition, or permanent degradation. Among numerous protein modifications, protein nitrosation and its functional relevance have emerged. Nitrosation generally initiates nitric oxide (NO) production in association with NO synthase. NO is conjugated to free thiol in the cysteine side chain (S-nitrosylation) and is propagated via the transnitrosylation mechanism. S-nitrosylation is a signaling pathway frequently involved in physiologic regulation. NO forms peroxynitrite in excessive oxidation conditions and induces tyrosine nitration, which is quite stable and is considered irreversible. Two main reducing systems are attributed to denitrosylation: glutathione and thioredoxin (TRX). Glutathione captures NO from S-nitrosylated protein and forms S-nitrosoglutathione (GSNO). The intracellular reducing system catalyzes GSNO into GSH again. TRX can remove NO-like glutathione and break down the disulfide bridge. Although NO is usually beneficial in the basal context, cumulative stress from chronic inflammation or oxidative insult produces a large amount of NO, which induces atypical protein nitrosation. Herein, we (1) provide a brief introduction to the nitrosation and denitrosylation processes, (2) discuss nitrosation-associated human diseases, and (3) discuss a possible denitrosylation strategy and its therapeutic applications.

show abstract

The role of S‐nitrosylation of kainate‐type of ionotropic glutamate receptor 2 in epilepsy induced by kainic acid

Cited by 9 publications

References 69 publications

Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children

Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children

Morphology of P2X3‐immunoreactive basket‐like afferent nerve endings surrounding serosal ganglia and close relationship with vesicular nucleotide transporter‐immunoreactive nerve fibers in the rat gastric antrum

Nitrosative Stress and Human Disease: Therapeutic Potential of Denitrosylation

Contact Info

Product

Resources

About