O-GlcNAcylation in immunity and inflammation: An intricate system (Review)

Yu, Li; Xie, Mingzheng; Men, Lili; Du, Junbao

doi:10.3892/ijmm.2019.4238

Cited by 45 publications

(40 citation statements)

References 119 publications

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“…The GlcNAcylation of transcription factors can regulate cellular processes and the addition of GlcN, GlcNAc, COS, and NACOS can improve these effects. The protein GlcNAcylation levels of different cells affect their cell responses through different pathways, including T/B cell activation [46,47], macrophage activation [48], chondrocyte inflammatory responses [49,50], and vascular endothelial inflammatory responses [18], among others.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of N-Acetyl Chitooligosaccharides on RAW264.7 Macrophages

Deng

et al. 2020

Marine Drugs

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The ongoing development of new production methods may lead to the commercialization of N-acetyl chitooligosaccharides (NACOS), such as chitosan oligosaccharides (COS). The bioactivity of NACOS, although not well detailed, differs from that of COS, as they have more acetyl groups than COS. We used two enzymatically produced NACOS with different molecular compositions and six NACOS (NACOS1–6) with a single degree of polymerization to verify their immunomodulatory effects on the RAW264.7 macrophage cell line. We aimed to identify any differences between COS and various NACOS with a single degree of polymerization. The results showed that NACOS had similar immune enhancement effects on RAW264.7 cells as COS, including the generation of reactive oxygen species (ROS), phagocytotic activity, and the production of pro-inflammation cytokines (IL-1β, IL-6, and TNF-α). However, unlike COS and lipopolysaccharide (LPS), NACOS1 and NACOS6 significantly inhibited nitric oxide (NO) production. Besides their immune enhancement effects, NACOS also significantly inhibited the LPS-induced RAW264.7 inflammatory response with some differences between various polymerization degrees. We confirmed that the NF-κB pathway is associated with the immunomodulatory effects of NACOS on RAW264.7 cells. This study could inform the application of NACOS with varying different degrees of polymerization in human health.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of N-Acetyl Chitooligosaccharides on RAW264.7 Macrophages

Deng

et al. 2020

Marine Drugs

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“…. Unlike phosphorylation, it is usually difficult to detect O-β-GlcNAc on proteins due to several technical and experimental limitations (Li et al, 2019;Zachara et al, 2015). To overcome this difficulty, several neural network methods have been used to predict O-β-GlcNAc on Ser/ Thr residues based on available experimental data and consensus sequences .…”

Section: Discussionmentioning

confidence: 99%

O-β-GlcNAcylation, Chloroquine and 2-Hydroxybenzohydrazine May Hamper SARS-CoV-2 entry to Human via Inhibition of ACE2 Phosphorylation at Ser787 but Also Induce Disruption of Virus-ACE2 Binding

Ahmad¹,

Shabbiri²,

Islam³

2020

Preprint

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The novel coronavirus COVID-19 disease is extremely contagious and has been spread worldwide. First COVID-19 case was identified in December, 2019 and within three months, more than one million affected cases and over 65,000 deaths have been reported. SARS-coronavirus 2 Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 22 April 2020 to the SARS CoV (Severe Acute Respiratory Syndrome corona virus) family. The SARS-CoV-2 enters the human body by binding its viral surface spike protein with the host angiotensinconverting enzyme 2 (ACE2) receptors and cause infection. To prevent the virus entry and its transmission in the human body, we focused on the two domains of ACE2: i) the N-terminal extracellular binding domain (18-740 residues) reported for coronavirus spike interaction, and ii) the C-terminal cytoplasmic region (762-805 residues) to prevent the virus transmission. Therefore, we proposed: i) inhibition of receptor binding domain (RBD) of SARS-CoV-2 and human ACE2 protein may prevent the virus entry to the host and ii) inhibition of phosphorylation at Ser-787 of ACE2 protein may prevent the transmission of the virus in the COVID-19 patients. In the past, the critical role of Ser 787 in human ACE2 protein has been experimentally verified in SARS-CoV transmission, that upon binding to the receptor, SARS-CoV induces CKII-mediated phosphorylation of ACE2 at Ser-787 that in-turn facilitate virus entry to host cells, followed by replication and activation of ACE2, initiates downstream signaling leading to lung fibrosis. Therefore, in this study, we have suggested post-translational modification (PTM) O-β-GlcNAcylation, and two compounds Chloroquine and 2-hydroxybenzohydrazine might share the common pathways to prevent the COVID-19 infection in human. The addition of O-β-GlcNAcylation at same or neighboring Ser/ Thr residues results in phosphorylation inhibition and a change in protein structural and functional confirmations. Thereby, using neural networking methods, we have identified Ser/ Thr residues in ACE2 that are potential sites for phosphorylation and / or O-β-GlcNAcylation. Molecular docking showed that UDP-GlcNAc has more binding affinity with Ser-787 than the phosphoryl group. Moreover, chloroquine and 2hydroxybenzohydrazine also showed great potential to bind at Ser-787 that may result in inhibition of Ser-787 phosphorylation and downstream signaling. Furthermore, O-β-GlcNAcylation, chloroquine and 2-hydroxybenzohydrazine showed their high affinity at ACE2-SARS-CoV-2receptor binding domain that may prevent the entry of SARS-CoV-2 into human body. In conclusion, inhibition of human ACE2 phosphorylation at Ser-787 and ACE2-SARS-CoV-2 binding domain could be promising targets against SARS-CoV-2 infection.

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“…A genome-wide de novo motif analysis of the chromatin regions displaying glutamine-linked changes in O-GlcNAcylation revealed an enrichment of the binding motif for SP1, a transcription factor that plays a central role in the regulation of pro-inflammatory responses. It has been shown in other cell systems that O-GlcNAcylation modulates SP1 activity and plays a role in hyperglycaemia-induced inflammation [29]. By immunoprecipitation of O-GlcNAc-modified proteins isolated from nuclei of human adipocytes, Petrus et al confirmed that glutamine reduced both SP1 O-GlcNAcylation and the expression of SP1-regulated target genes.…”

Section: The Immunomodulatory Potential Of Glutamine In Adipose Tissuementioning

confidence: 99%

Glutamine metabolism in adipocytes: a bona fide epigenetic modulator of inflammation

et al. 2020

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A chronic low-grade inflammation of white adipose tissue (WAT) is one of the hallmarks of obesity and is proposed to contribute to insulin resistance and type 2 diabetes. Despite this, the causal mechanisms underlying WAT inflammation remain unclear. Based on metabolomic analyses of human WAT, Petrus et al. showed that the amino acid glutamine was the most markedly reduced polar metabolite in the obese state. Reduced glutamine levels in adipocytes induce an increase of Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels via induction of glycolysis and the hexosamine biosynthetic pathways. This promotes nuclear O-GlcNAcylation, a posttranslational modification that activates the transcription of pro-inflammatory genes. Conversely, glutamine supplementation in vitro and in vivo, reversed these effects. Altogether, dysregulation of intracellular glutamine metabolism in WAT establishes an epigenetic link between adipocytes and inflammation. This commentary discusses these findings and their possibly therapeutic relevance in relation to insulin resistance and type 2 diabetes.

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O-GlcNAcylation in immunity and inflammation: An intricate system (Review)

Cited by 45 publications

References 119 publications

Immunomodulatory Effects of N-Acetyl Chitooligosaccharides on RAW264.7 Macrophages

Immunomodulatory Effects of N-Acetyl Chitooligosaccharides on RAW264.7 Macrophages

<strong>O-β-GlcNAcylation,</strong><strong> Chloroquine and </strong><strong>2-Hydroxybenzohydrazine May Hamper SARS-CoV-2 entry to Human via Inhibition of ACE2 Phosphorylation at Ser787 but Also Induce Disruption of Virus-ACE2 Binding</strong>

Glutamine metabolism in adipocytes: a bona fide epigenetic modulator of inflammation

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O-GlcNAcylation in immunity and inflammation: An intricate system (Review)

Cited by 45 publications

References 119 publications

Immunomodulatory Effects of N-Acetyl Chitooligosaccharides on RAW264.7 Macrophages

Immunomodulatory Effects of N-Acetyl Chitooligosaccharides on RAW264.7 Macrophages

<strong>O-&beta;-GlcNAcylation,</strong><strong> Chloroquine and </strong><strong>2-Hydroxybenzohydrazine May Hamper SARS-CoV-2 entry to Human via Inhibition of ACE2 Phosphorylation at Ser787 but Also Induce Disruption of Virus-ACE2 Binding</strong>

Glutamine metabolism in adipocytes: a bona fide epigenetic modulator of inflammation

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Resources

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<strong>O-β-GlcNAcylation,</strong><strong> Chloroquine and </strong><strong>2-Hydroxybenzohydrazine May Hamper SARS-CoV-2 entry to Human via Inhibition of ACE2 Phosphorylation at Ser787 but Also Induce Disruption of Virus-ACE2 Binding</strong>