High-mannose Type Oligosaccharide-dependent Apoptosis in U937 Cells Induced by Pradimicin, a Mannose-binding Antibiotic.

Oki, Taikan; Yamazaki, Yasuharu; Nomura, Nobuhiro; Furumai, Tamotsu; Igarashi, Yasuhiro

doi:10.7164/antibiotics.52.449

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…Up-regulated AMPA (␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-kainate receptors can allow excessive Ca 2ϩ ions to enter through NMDA receptor-gated ion channels (36), which could in turn react with reactive oxygen species (ROS) and trigger apoptosis (37). This potential increase in vulnerability to apoptosis may be amplified by the dysregulation in growth factors we have observed in the same brains, particularly the FGF system (14).…”

Section: Discussionmentioning

confidence: 88%

Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression

Choudary

Molnar

Evans

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

581

393

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Abnormalities in L-glutamic acid (glutamate) and GABA signal transmission have been postulated to play a role in depression, but little is known about the underlying molecular determinants and neural mechanisms. Microarray analysis of specific areas of cerebral cortex from individuals who had suffered from major depressive disorder demonstrated significant down-regulation of SLC1A2 and SLC1A3, two key members of the glutamate͞neutral amino acid transporter protein family, SLC1. Similarly, expression of L-glutamate-ammonia ligase, the enzyme that converts glutamate to nontoxic glutamine was significantly decreased. Together, these changes could elevate levels of extracellular glutamate considerably, which is potentially neurotoxic and can affect the efficiency of glutamate signaling. The astroglial distribution of the two glutamate transporters and L-glutamate-ammonia ligase strongly links glia to the pathophysiology of depression and challenges the conventional notion that depression is solely a neuronal disorder. The same cortical areas displayed concomitant up-regulation of several glutamate and GABA A receptor subunits, of which GABA A␣1 and GABAA␤3 showed selectivity for individuals who had died by suicide, indicating their potential utility as biomarkers of suicidality. These findings point to previously undiscovered molecular underpinnings of the pathophysiology of major depression and offer potentially new pharmacological targets for treating depression.bipolar disorder ͉ GABAA receptors ͉ glutamate transporters ͉ major depression ͉ suicide C linical depression, the phenotypic hallmark of the two leading mood disorders [major depressive disorder (MDD) and bipolar affective disorder (BPD)], is the most common psychiatric illness. It affects Ϸ121 million people worldwide, with 10-20% of women and 5-12% of men estimated to experience a depressive episode in any 1-year period, and with evidence of suicidality in 15% of those affected (ref.

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Section: Discussionmentioning

confidence: 88%

Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression

Choudary

Molnar

Evans

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

581

393

View full text Add to dashboard Cite

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“…The most abundantly expressed N‐linked glycan on CD11b, representing approximately 22% of total N‐glycans (blue shading, supplemental Table 1), was predicted to be an uncommon terminal high mannose‐type oligosaccharide (Man 9 GlcNAc 2, m/z 2396.3, black box Figure D). These complex glycans with non‐reducing end mannose residues represent ligands for Galanthus Nivalis lectin (GNA) and mannose macrophage receptor (MMR) In addition, more common mannose‐containing glycans were detected on CD11b (Figure D, green boxes). Several biantennary galactosylated N‐glycans (blue boxes, Figure D) accounting for approximately 18% of all predicted N‐glycans on CD11b (yellow shading, Supplemental Table 1) were also identified.…”

Section: Resultsmentioning

confidence: 99%

Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18

et al. 2019

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Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens. However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease. The glycoprotein CD11b/CD18 plays a well‐described role in regulating PMN transepithelial migration and PMN inflammatory functions. Previous studies have demonstrated that targeting of the N‐linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM). Given evidence of glycosylation‐dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs. Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N‐glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin. Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis. Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN‐associated tissue damage in chronic inflammatory diseases.

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“…1D). These complex glycans with non-reducing end mannose residues represent ligands for Galanthus Nivalis lectin (GNA) (42) and mannose macrophage receptor (MMR) (43,44). In addition, more common mannose containing glycans were detected on CD11b (Fig.…”

Section: Purification and Maldi-tof Mass Spectrometry (Ms) Analysis Of Human Cd11b/cd18mentioning

confidence: 99%

Regulation of Neutrophil Function by Selective Targeting of Glycan Epitopes Expressed on the Integrin CD11b/CD18

et al. 2020

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Polymorphonuclear neutrophils (PMN) play a critical role in the innate immune response to invading pathogens. However, dysregulated mucosal trafficking of PMN and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease and chronic obstructive pulmonary disease. The glycoprotein CD11b/CD18 plays a well described role in regulating PMN transepithelial migration and PMN inflammatory functions. Previous studies have demonstrated that targeting of the N‐linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM). Given evidence of glycosylation dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMN. MS analyses revealed a surprising lack of sialylation on CD11b glycans. Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis (GNA) lectin and biantennary galactosylated N‐glycans recognized by the Phaseolus Vulgaris erythroagglutinin (PHA‐E) lectin. Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis. Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN associated tissue damage in chronic inflammatory diseases. Support or Funding Information This work was supported by the Crohn’s and colitis foundation (SRA # 544596)

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High-mannose Type Oligosaccharide-dependent Apoptosis in U937 Cells Induced by Pradimicin, a Mannose-binding Antibiotic.

Cited by 10 publications

References 16 publications

Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression

Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression

Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18

Regulation of Neutrophil Function by Selective Targeting of Glycan Epitopes Expressed on the Integrin CD11b/CD18

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