Memantine protects blood–brain barrier integrity and attenuates neurological deficits through inhibiting nitric oxide synthase ser1412 phosphorylation in intracerebral hemorrhage rats: involvement of peroxynitrite-related matrix metalloproteinase-9/NLRP3 inflammasome activation

Chen, Xiaowei; Xu, Xiang; Xie, Tian; Chen, Zhijun; Mou, Yu; Gao, Zixu; Xie, Xun; Song, Min Seok; Huang, Hui; Gao, Zhiqiang; Chen, Min

doi:10.1097/wnr.0000000000001577

Cited by 12 publications

(6 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We detected hyperphosphorylation events in the flavin mononucleotide–binding domain in the SON and NIL as a result of WD, where increased phosphorylation at S847 in the NIL, but not the SON, has been shown to reduce NOS1 activity by inhibiting the binding of Ca 2+ to the calmodulin domain ( 73 , 74 ). In addition, NOS1 phosphorylation at S1412 in the NADPH-binding domain (hyperphosphorylated in SON, but not NIL) has been shown to increase the activity of NOS1 ( 75 , 76 ). It has been suggested that hyperosmotic stimulation induces NO production in MCNs in the SON ( 77 , 78 ), reducing AVP and OXT secretion as a feedback compensatory mechanism to prevent oversecretion of these peptides ( 79 ).…”

Section: Discussionmentioning

confidence: 99%

Translational and Posttranslational Dynamics in a Model Peptidergic System

Bárez-López¹,

Mecawi²,

Bryan³

et al. 2023

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Translational and Posttranslational Dynamics in a Model Peptidergic System

Bárez-López¹,

Mecawi²,

Bryan³

et al. 2023

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

“…We detected hyperphosphorylation events in the flavin mononucleotide (FMN)-binding domain in the SON and NIL as a result of WD, where increased phosphorylation at S847 in the NIL, but not the SON, has been shown to reduce NOS1 activity by inhibiting the binding of Ca 2+ to the calmodulin domain (Hayashi et al, 1999; Komeima et al, 2000). In addition, NOS1 phosphorylation at S1412 in the NADPH-binding domain (hyperphosphorylated in SON, but not NIL) has been shown to increase the activity of NOS1 (Chen et al, 2021; Khan et al, 2015). It has been suggested that hyperosmotic stimulation induces NO production in MCNs in the SON (da Silva et al, 2013; Reis et al, 2015) reducing AVP and OXT secretion as a feedback compensatory mechanism to prevent over-secretion of these peptides (Pires da Silva et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Multiomic deep delve of synthesis and secretion processes in a model peptidergic system

Bárez-López

Mecawi

Bryan

et al. 2022

Preprint

View full text Add to dashboard Cite

The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus (SON) whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganisation of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and become hyperphosphorylated following stimulation. By multi-omic integration of transcriptome and proteomic data we identify changes to proteins present in afferent inputs to this nucleus.

show abstract

“…For example, pioglitazone, edaravone and adiponectin significantly reduced brain edema and attenuated neurological deficits after ICH, as well as decreased the expression of IL-1β, IL-18, caspase-1 and NF-κB through suppressing the expression of NLRP3 [8,28,29]. Glibenclamide markedly reduced the neurological deficit and brain edema after ICH by decreasing the expression of ASC and caspase-1 and suppressing the activation of the NLRP3 inflammasome to maintain BBB integrity [30]. Memantine reduces ONOO-production by inhibiting neuronal nitric oxide synthase (nNOS) phosphorylation at ser1412, which further inhibits MMP-9 expression and NLRP3 inflammasome activation, protecting the blood-brain barrier integrity and alleviating neurological deficits in ICH rats [31].…”

Section: Modulation Of Nlrp3 Inflammasome Activity As a Therapeutic S...mentioning

confidence: 98%

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

Zhang

Flynn

et al. 2022

Nutrients

View full text Add to dashboard Cite

The pathophysiological process of intracerebral hemorrhage (ICH) is very complex, involving various mechanisms such as apoptosis, oxidative stress and inflammation. As one of the key factors, the inflammatory response is responsible for the pathological process of acute brain injury and is associated with the prognosis of patients. Abnormal or dysregulated inflammatory responses after ICH can aggravate cell damage in the injured brain tissue. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex distributed in the cytosol, which can be triggered by multiple signals. The NLRP3 inflammasome is activated after ICH, thus promoting neuroinflammation and aggravating brain edema. In addition, there is evidence that the gut microbiota is crucial in the activation of the NLRP3 inflammasome. The gut microbiota plays a key role in a variety of CNS disorders. Changes in the diversity and species of the gut microbiota affect neuroinflammation through the activation of the NLRP3 inflammasome and the release of inflammatory cytokines. In turn, the gut microbiota composition can be influenced by the activation of the NLRP3 inflammasome. Thereby, the regulation of the microbe–gut–brain axis via the NLRP3 inflammasome may serve as a novel idea for protecting against secondary brain injury (SBI) in ICH patients. Here, we review the recent evidence on the functions of the NLRP3 inflammasome and the gut microbiota in ICH, as well as their interactions, during the pathological process of ICH.

show abstract

Memantine protects blood–brain barrier integrity and attenuates neurological deficits through inhibiting nitric oxide synthase ser1412 phosphorylation in intracerebral hemorrhage rats: involvement of peroxynitrite-related matrix metalloproteinase-9/NLRP3 inflammasome activation

Abstract: Supplemental Digital Content is available in the text.

Cited by 12 publications

References 65 publications

Translational and Posttranslational Dynamics in a Model Peptidergic System

Translational and Posttranslational Dynamics in a Model Peptidergic System

Multiomic deep delve of synthesis and secretion processes in a model peptidergic system

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

Contact Info

Product

Resources

About