Effects of N-glycan processing inhibitors on signaling events and induction of apoptosis in galectin-1-stimulated Jurkat T lymphocytes

Walzel, Hermann; Fahmi, Abdelgawad A.; El-Desouky, Mohamed A.; Abou-Eladab, Ehab F.; Waitz, Grit; Brock, Josef; Tiedge, Markus

doi:10.1093/glycob/cwl037

Cited by 30 publications

(22 citation statements)

References 49 publications

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“…Susceptibility to gal-1 induced cell death is modulated by the expression of speciWc glycosyltransferases and depends upon the glycosylation status of the cells (Amano et al 2003;Walzel et al 2006). Addition of 2,6-linked sialic acid to Gal 1-4Glc-NAc sequences by ST6Gal I sialyltransferase inhibits gal-1 binding to its preferred disaccharidic recognition structure.…”

Section: Discussionmentioning

confidence: 99%

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Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes

Brandt

Büchse

Abou-Eladab

et al. 2008

Histochem Cell Biol

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Galectin-1 (gal-1), a member of the family of beta-galactoside binding proteins, participates in several biological processes such as immunomodulation, cell adhesion, regulation of cell growth and apoptosis. The aim of this study was to investigate whether gal-1 interferes with the Fas (Apo-1/CD95)-associated apoptosis cascade in the T-cell lines Jurkat and MOLT-4. Gal-1 and an Apo-1 monoclonal antibody (mAb) induced DNA-fragmentation in Jurkat T-cells whereas MOLT-4 cells were resistant. Gal-1 stimulated DNA-fragmentation could be efficiently inhibited by caspase-8 inhibitor II (Z-IETD-FMK) and a neutralizing Fas mAb. Fas could be identified as a target for gal-1 recognition as demonstrated by immunofluorescence staining, binding of the receptor glycoprotein to immobilized gal-1 and analyses by immunoblotting as well as by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gal-1 stimulates the activation and proteolytic processing of procaspase-8 and downstream procaspase-3 in Jurkat-T cells. Inhibition of gal-1 induced procaspase-8 activation by a neutralizing Fas mAb strongly suggests that gal-1 recognition of Fas is associated with caspase-8 activation. Our data provide the first experimental evidence for targeting of gal-1 to glycotopes on Fas and the subsequent activation of the apoptotic death-receptor pathway.

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Section: Discussionmentioning

confidence: 99%

“…Notably, the increase of p43/41 occurred prior to the onset of DNA-fragmentation (Walzel et al 2006). Furthermore, procaspase-8 processing was blocked by caspase-8 inhibitor II (Z-IETD-FMK, 40 M) and by lactose at 30 mM (Fig.…”

Section: Gal-1 Induces Initiator Procaspase-8 Activation In Jurkat E6mentioning

confidence: 98%

Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes

Brandt

Büchse

Abou-Eladab

et al. 2008

Histochem Cell Biol

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“…1-deoxymannojirimycin (DMNJ), in contrast, inhibits a-mannosidase I, leading to the accumulation of high mannose-type N-glycan precursor that cannot be processed further into complex N-glycans. N-glycan inhibition with DMNJ can be verified by reduced staining with Phaseolus vulgaris agglutinin (PHA) that binds complex N-glycans (30,32). Inhibition of O-glycan elongation with benzylaGalNAc during T cell activation resulted in a concentration-dependent increase in the percentage of SnL + CD4 + T cells (Fig.…”

Section: Snl Requires N-linked Glycan Biosynthesismentioning

confidence: 98%

Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3− T Cells with a Distinct Activation and Glycosylation Profile

Kidder

Richards

Ziltener³

et al. 2013

The Journal of Immunology

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Sialoadhesin (Sn) is a sialic acid–binding Ig-like lectin expressed selectively on macrophage subsets. In a model of experimental autoimmune encephalomyelitis, Sn interacted with sialylated ligands expressed selectively on CD4+Foxp3+ regulatory T cells (Tregs) and inhibited their proliferation. In this study, we examined the induction of Sn ligands (SnL) on all splenic CD4+ T cells following in vitro activation. Most CD4+ Tregs strongly upregulated SnL, whereas only a small subset of ∼20% CD4+Foxp3− T cells (effector T cells [Teffs]) upregulated SnL. SnL+ Teffs displayed higher levels of activation markers CD25 and CD69, exhibited increased proliferation, and produced higher amounts of IL-2 and IFN-γ than corresponding SnL− Teffs. Coculture of activated Teffs with Sn+ macrophages or Sn+ Chinese hamster ovary cells resulted in increased cell death, suggesting a regulatory role for Sn–SnL interactions. The key importance of α2,3-sialylation in SnL expression was demonstrated by increased binding of α2,3-linkage–specific Maackia amurensis lectin, increased expression of α2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an α2,3-linkage–specific sialidase. The induction of SnL on activated CD4+ T cells was dependent on N-glycan rather than O-glycan biosynthesis and independent of the mucin-like molecules CD43 and P-selectin glycoprotein ligand-1, previously implicated in Sn interactions. Induction of ligands on CD4+Foxp3− Teffs was also observed in vivo using the New Zealand Black × New Zealand White F1 murine model of spontaneous lupus and SnL levels on Teffs correlated strongly with the degree of proteinuria. Collectively, these data indicate that SnL is a novel marker of activated CD4+ Teffs that are implicated in the pathogenesis of autoimmune diseases.

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“…Binding to glycoconjugates acting as cargo receptors is an integral part of the export pathway across the plasma membrane (Seelenmeyer et al 2005). Functional gal-1 is a homodimer of noncovalently associated 14 kDa subunits with two CRDs which recognises and crosslinks several cell surface glycoproteins on T cells including the signalling proteins CD2, CD3, CD7, CD43 and CD45 (Perillo et al 1995;Walzel et al 1999Walzel et al , 2000Walzel et al , 2006Pace et al 2000). Exogenous gal-1 induces in vitro the redistribution of some of these signalling proteins into segregated microdomains within the plasma membrane (Pace et al 1999;Brewer 2002).…”

Section: Introductionmentioning

confidence: 99%

Galectin-1 induced activation of the mitochondrial apoptotic pathway: evidence for a connection between death-receptor and mitochondrial pathways in human Jurkat T lymphocytes

Lange

Brandt

Tiedge

et al. 2009

Histochem Cell Biol

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Galectin-1 (gal-1) triggers T cell death by several distinct intracellular pathways including the activation of the death-receptor pathway. The aim of this study was to investigate whether gal-1 induced activation of the death-receptor pathway in Jurkat T lymphocytes mediates apoptosis via the mitochondrial pathway linked by truncated Bid (tBid). We demonstrate that gal-1 induced proteolytic cleavage of the death agonist Bid, a member of the Bcl-2/Bcl-xL family and a substrate of activated caspase-8, was inhibited by caspase-8 inhibitor II (Z-IETD-FMK). Downstream of Bid, gal-1 stimulated mitochondrial cytochrome c release as well as the activation and proteolytic processing of initiator procaspase-9 were effectively decreased by caspase-8 inhibitor II. Blocking of gal-1 induced cleavage of effector procaspase-3 by caspase-8 inhibitor II as well as by caspase-9 inhibitors I (Z-LEHD-FMK) and III (Ac-LEHD-CMK) indicates that receptor and mitochondrial pathways converged in procaspase-3 activation and contribute to proteolytic processing of effector procaspase-6 and -7. Western blot analyses and immunofluorescence staining revealed that exposure of Jurkat T cells to gal-1 resulted in the cleavage of the DNA-repair enzyme poly (ADP-ribose) polymerase, cytoskeletal alpha-fodrin, and nuclear lamin A as substrates of activated caspases. Our data demonstrate that Bid provides a connection between the death receptor and the mitochondrial pathway of gal-1 induced apoptosis in human Jurkat T lymphocytes.

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Effects of N-glycan processing inhibitors on signaling events and induction of apoptosis in galectin-1-stimulated Jurkat T lymphocytes

Cited by 30 publications

References 49 publications

Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes

Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes

Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3− T Cells with a Distinct Activation and Glycosylation Profile

Galectin-1 induced activation of the mitochondrial apoptotic pathway: evidence for a connection between death-receptor and mitochondrial pathways in human Jurkat T lymphocytes

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