Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Zeng, Xianzhang; Ren, Hongliang; Zhu, Yu; Zhang, Ruru; Xue, Xinxin; Tao, Tao; Xi, Hongjie

doi:10.1159/000494243

Cited by 16 publications

(17 citation statements)

References 46 publications

(50 reference statements)

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“…Here, we expand our understanding of the neuroinflammatory phenotype induced by noise by demonstrating a clear involvement of microglia, the major immune cell of the brain. As tissue resident macrophages, microglia also express NOX-2 and produce ROS in a wide variety of pathologies in both retinal and cerebral tissues [14,56,76]. Interestingly, the retina contains both LysM + peripheral macrophages and central microglia [36], offering a possible explanation for the partial normalization of endothelial function and ROS generation we recorded in the retinal vessels of this study.…”

Section: Discussionmentioning

confidence: 53%

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

et al. 2021

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Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6G−Ly6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.

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Section: Discussionmentioning

confidence: 53%

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

et al. 2021

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“…The cytosolic complex made up of p47, p67, and p40 phox proteins translocate to the membrane and dock with the membrane subunits in response to stimulation . It is well known that gp91phox protein is the catalytic core of NADPH oxidase and mainly responsible for the formation of ROS in cells . A previous study also showed the upregulation of gp91phox expression was associated with the increase in the activity of NADPH oxidase in response to LPS .…”

Section: Discussionmentioning

confidence: 97%

A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

Hou

Zhang

et al. 2019

Molecular Nutrition Food Res

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Scope The anti‐neuroinflammatory effect of a novel quinolyl‐substituted analogue of resveratrol (RV01) on lipopolysaccharide (LPS)‐induced microglial activation is investigated, as well as the possible underlying mechanisms. Methods and results Cell viability is measured using an MTT assay. Nitric oxide (NO) release is determined by nitrite assay. The interaction between RV01 and inducible nitric oxide synthase (iNOS) is studied using molecular docking. Free radical scavenging activity and reactive oxygen species (ROS) production are determined by DPPH reduction assay and DCFH‐DA assay. Pretreatment with RV01 (1–30 µm) prior to LPS (1 µg mL–1) stimulation decreased NO release and iNOS expression without observable cytotoxicity. RV01 reduced the mRNA levels and secretion of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). RV01 also inhibited LPS‐induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Furthermore, RV01 decreases the protein expression of toll‐like receptor 4 (TLR4) and inhibits the LPS‐induced activation of the mitogen‐activated protein kinase (MAPK) and nuclear transcription factor‐κB (NF‐κB) signaling pathways. Additionally, conditioned medium from microglia co‐treated with LPS and RV01 alleviates the death of SH‐SY5Y cells induced by conditioned medium from activated N9 microglial cells. Lastly, a mouse neuroinflammation model is further used to confirm the effect of RV01 in vivo. Conclusion These results show that RV01 suppresses microglia‐mediated neuroinflammation and protects neurons from inflammatory damage, which indicates that RV01 has great potential as a nutritional preventive strategy for neuroinflammation‐related diseases.

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“…In astroglial cells, metabolic stress alters glutamate metabolism, mitochondrial activity/redox balance, inflammatory response, release of trophic factors, and different signaling pathways [ 34 – 36 ]. Glucose-related metabolic stress also affects microglia and oligodendrocytes/OPCs, promoting microglial activation and contributing to inflammatory and oxidative injuries to neurons [ 37 , 38 ]. Hypoglycemia inhibits oligodendrocyte development and differentiation, in addition to trigger apoptosis in OPCs [ 39 ], while glucose-oxygen deprivation causes intracellular lactate accumulation and acidosis [ 40 ].…”

Section: Neurochemical Changes and Molecular Mechanisms Associated With Gliotoxicitymentioning

confidence: 99%

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells

et al. 2021

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Glial cells (astrocytes, oligodendrocytes and microglia) are critical for the central nervous system (CNS) in both physiological and pathological conditions. With this in mind, several studies have indicated that glial cells play key roles in the development and progression of CNS diseases. In this sense, gliotoxicity can be referred as the cellular, molecular, and neurochemical changes that can mediate toxic effects or ultimately lead to impairment of the ability of glial cells to protect neurons and/or other glial cells. On the other hand, glioprotection is associated with specific responses of glial cells, by which they can protect themselves as well as neurons, resulting in an overall improvement of the CNS functioning. In addition, gliotoxic events, including metabolic stresses, inflammation, excitotoxicity, and oxidative stress, as well as their related mechanisms, are strongly associated with the pathogenesis of neurological, psychiatric and infectious diseases. However, glioprotective molecules can prevent or improve these glial dysfunctions, representing glial cells-targeting therapies. Therefore, this review will provide a brief summary of types and functions of glial cells and point out cellular and molecular mechanisms associated with gliotoxicity and glioprotection, potential glioprotective molecules and their mechanisms, as well as gliotherapy. In summary, we expect to address the relevance of gliotoxicity and glioprotection in the CNS homeostasis and diseases.

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Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Cited by 16 publications

References 46 publications

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects

A Novel Quinolyl‐Substituted Analogue of Resveratrol Inhibits LPS‐Induced Inflammatory Responses in Microglial Cells by Blocking the NF‐κB/MAPK Signaling Pathways

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells

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