Effect of Xenon on the Phosphorylation of Glycogen Synthase Kinase 3β and Antioxidant Enzymes in Rat Brain

Кузовлев, А. Н.; Shpichko, A. I.; Рыжков, И. А.; Гребенчиков, О. А.; Шабанов, А. К.; Хусаинов, Ш. Ж.; Цоколаева, З. И.; Lobanov, A. V.

doi:10.23934/2223-9022-2020-9-4-564-572

Cited by 5 publications

(1 citation statement)

References 31 publications

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“…In one study, a 30-min exposure of non-injured rats to 55% xenon resulted in increased expression of GSK3β, a Bax inhibitor, in brain tissues (Kuzovlev et al, 2021).…”

Section: Downstream Proteins Involved In Cell Survival Signalingmentioning

confidence: 99%

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

McGuigan,

Marie,

O'Bryan

et al. 2023

Front. Neurosci.

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IntroductionXenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in human studies of neurological injury remains elusive. Previous reviews of xenon's method of action have not been performed in a systematic manner. The aim of this review is to provide a comprehensive summary of the evidence underlying the cellular interactions responsible for two phenomena associated with xenon administration: anesthesia and neuroprotection.MethodsA systematic review of the preclinical literature was carried out according to the PRISMA guidelines and a review protocol was registered with PROSPERO. The review included both in vitro models of the central nervous system and mammalian in vivo studies. The search was performed on 27th May 2022 in the following databases: Ovid Medline, Ovid Embase, Ovid Emcare, APA PsycInfo, and Web of Science. A risk of bias assessment was performed utilizing the Office of Health Assessment and Translation tool. Given the heterogeneity of the outcome data, a narrative synthesis was performed.ResultsThe review identified 69 articles describing 638 individual experiments in which a hypothesis was tested regarding the interaction of xenon with cellular targets including: membrane bound proteins, intracellular signaling cascades and transcription factors. Xenon has both common and subtype specific interactions with ionotropic glutamate receptors. Xenon also influences the release of inhibitory neurotransmitters and influences multiple other ligand gated and non-ligand gated membrane bound proteins. The review identified several intracellular signaling pathways and gene transcription factors that are influenced by xenon administration and might contribute to anesthesia and neuroprotection.DiscussionThe nature of xenon NMDA receptor antagonism, and its range of additional cellular targets, distinguishes it from other NMDA antagonists such as ketamine and nitrous oxide. This is reflected in the distinct behavioral and electrophysiological characteristics of xenon. Xenon influences multiple overlapping cellular processes, both at the cell membrane and within the cell, that promote cell survival. It is hoped that identification of the underlying cellular targets of xenon might aid the development of potential therapeutics for neurological injury and improve the clinical utilization of xenon.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: 336871.

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“…In one study, a 30-min exposure of non-injured rats to 55% xenon resulted in increased expression of GSK3β, a Bax inhibitor, in brain tissues (Kuzovlev et al, 2021).…”

Section: Downstream Proteins Involved In Cell Survival Signalingmentioning

confidence: 99%

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

McGuigan,

Marie,

O'Bryan

et al. 2023

Front. Neurosci.

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The Effect of Xenon on the Activity of Glycogen Synthase Kinase-Зβ in the Perifocal Zone of Ischemic Cerebral Infarction (Experimental Study)

Ershov

Krukov

Antonova³

et al. 2023

Obŝaâ reanimatologiâ

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Aim of the study. To determine the effects of xenon exposure at a dose of 0.5 MAC of different duration on the content and enzyme-inactivating phosphorylation of the glycogen synthase kinase-3β (GSK3β) in the perifocal zone of ischemic cerebral infarction in an experimental setting.Materials and methods. The Long method was used for modelling brain ischemia/reperfusion in 39 rats weighing 300-350 g. Study group animals was exposed to xenon at a dose of 0.5 MAC during 30, 60 and 120 minutes whereas control group animals received an oxygen-air mixture. Sham-operated animals served as a comparison group. The levels of GSK3β and phospho-GSK3β in brain homogenates were determined by blotting using specific antibodies.Results. In ischemic stroke model, the content of GSK3β did not significantly change in control animals compared to comparison group. However, control group animals exhibited significant (2.7-fold, P<0.001) decrease in the content of its phospho-GSK3β in the perifocal zone of ischemic cerebral infarction. Inhalation of 0.5 MAC xenon during 30 minutes did not lead to an increase in phosphorylation of the GSK3β enzyme (P=0.9), however, 60 and 120 minutes of 0.5 MAC xenon exposures resulted in the increase in phosphorylated form of the enzyme by a factor of 2.1 (P=0.005) and 2.3 (P=0.001), respectively, compared to the control group.Conclusion. The results reveal a possible molecular mechanism (i. e., execution of neuroprotective and anti-inflammatory effects of xenon due to GSK-Зβ inactivation) and show the prospects for using 60 and 120 minutes of 0.5 MAC xenon exposures in ischemic brain damage after a stroke, traumatic brain injury and other brain lesions.

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Effect of Xenon on Proinflammatory Activation and Apoptosis of Human Neutrophils Under Ex Vivo Conditions

Гребенчиков

Шабанов²,

Nikolayev

et al. 2021

Neotložnaâ med. pomoŝʹ

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Background. The syndrome of systemic inflammatory response, which underlies the damaging effect of factors of infectious and non-infectious genesis, may cause multiple organ failure. The degree of its severity is determined, among other things, by the activation of neutrophils. The paper highlights new mechanisms of the anti-inflammatory action of the inhalation anesthetic xenon, mediated by a decrease in the ability of neutrophils to pro-inflammatory response.Aim of study. To evaluate the effect of xenon on the activation of human neutrophils under ex vivo conditions.Material AND methods. We studied the effect of xenon inhalation on reduction of the ability of neutrophils to be activated proinflammatory by reduced expression of adhesion molecules CD11b and CD66b on the surface of neutrophils and on the phosphorylation of proinflammatory kinases: ERK 1/2 and kinase — p38 in neutrophils of healthy volunteers.Results. The use of xenon at a dose of 30 vol. % within 60 minutes in healthy volunteers statistically significantly reduces the ability of neutrophils to proinflammatory activation. The addition of lipopolysaccharide (LPS) to the incubation medium of neutrophils causes their pronounced activation, statistically significantly increasing the phosphorylation of key proinflammatory neutrophil kinases ERK1/2 and kinase p38. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on LPS-stimulated neutrophils, decreasing their activation by inhibiting pro-inflammatory kinase ERK1/2 and pro-inflammatory MAP kinase p38.Conclusion. The actual study, performed on isolated neutrophils from volunteers who underwent xenon inhalation, revealed the anti-inflammatory properties of the inert gas xenon, which, in our opinion, may have a direct relationship to the identification of the mechanism of its neuroprotective properties. Thus, the research results available today suggest that xenon has a pronounced pleiotropic mechanism of brain protection. This is a partial blockade of NMDA receptors, and phosphorylation of the enzyme glycogen synthase-3β, and limitation of the inflammatory activation of neutrophils.Findings. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on neutrophils stimulated by lipopolysaccharides, decreasing their activation by inhibiting proinflammatory ERK 1/2 kinase and proinflammatory MAP kinase p38, as well as reducing the expression of markers of activation and degranulation CD11b and CD66b on the surface of neutrophils. Stimulation by lipopolysaccharides statistically significantly reduces spontaneous apoptosis of neutrophils, while xenon increases the ability of neutrophils to apoptosis, which is likely to contribute to the resolution of inflammation.

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Effect of Xenon on the Phosphorylation of Glycogen Synthase Kinase 3β and Antioxidant Enzymes in Rat Brain

Cited by 5 publications

References 31 publications

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

The Effect of Xenon on the Activity of Glycogen Synthase Kinase-Зβ in the Perifocal Zone of Ischemic Cerebral Infarction (Experimental Study)

Effect of Xenon on Proinflammatory Activation and Apoptosis of Human Neutrophils Under Ex Vivo Conditions

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