CD40 ligand, Bcl-2, and Bcl-xL spare group I Burkitt lymphoma cells from CD77-directed killing via Verotoxin-1 B chain but fail to protect against the holotoxin

Gordon, John; Challa, Anita; Levens, J M; Gregory, C. D.; Williams, JM; Armitage, R J; Jp, Cook; Roberts, Lewis R.; Lord, Janet M.

doi:10.1038/sj.cdd.4400710

Cited by 33 publications

(37 citation statements)

References 57 publications

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“…Globotriaosyl ceramide (Gal␣(1-4)-Gal␤(1-4)-Glc␤1-ceramide) is differentially organized in glycolipid-enriched microdomains in mammalian membranes (44). After internalization of the holotoxin by receptor-mediated endocytosis, verotoxin inhibits protein synthesis resulting in necrosis and/or apoptosis (45)(46)(47). Whether RsAFP2-induced fungal growth arrest is a result of the induced membrane permeabilization or results from its interaction with a putative intracellular target is currently not known.…”

Section: Discussionmentioning

confidence: 99%

Defensins from Insects and Plants Interact with Fungal Glucosylceramides

Thevissen¹,

Warnecke

François³

et al. 2004

Journal of Biological Chemistry

328

310

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Growth of the yeast species Candida albicans andPichia pastoris is inhibited by RsAFP2, a plant defensin isolated from radish seed (Raphanus sativus), at micromolar concentrations. In contrast, gcs-deletion mutants of both yeast species are resistant toward RsAFP2. GCS genes encode UDP-glucose:ceramide glucosyltransferases, which catalyze the final step in the biosynthesis of the membrane lipid glucosylceramide. In an enzymelinked immunosorbent assay-based binding assay, RsAFP2 was found to interact with glucosylceramides isolated from P. pastoris but not with soybean nor human glucosylceramides. Furthermore, the P. pastoris parental strain is sensitive toward RsAFP2-induced membrane permeabilization, whereas the corresponding gcs-deletion mutant is highly resistant to RsAFP2-mediated membrane permeabilization. A model for the mode of action of RsAFP2 is presented in which all of these findings are linked. Similarly to RsAFP2, heliomicin, a defensin-like peptide from the insect Heliothis virescens, is active on C. albicans and P. pastoris parental strains but displays no activity on the gcs-deletion mutants of both yeast species. Furthermore, heliomicin interacts with glucosylceramides isolated from P. pastoris and soybean but not with human glucosylceramides. These data indicate that structurally homologous antifungal peptides present in species from different eukaryotic kingdoms interact with the same target in the fungal plasma membrane, namely glucosylceramides, and as such support the hypothesis that defensins from plants and insects have evolved from a single precursor.

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Section: Discussionmentioning

confidence: 99%

Defensins from Insects and Plants Interact with Fungal Glucosylceramides

Thevissen¹,

Warnecke

François³

et al. 2004

Journal of Biological Chemistry

328

310

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“…In our present study, we used only the nontoxic STxB. It has been shown by several studies that STxB is capable of apoptosis induction in Burkitt's lymphoma cells, although it is not able to inhibit protein synthesis (33,36,38).…”

Section: Discussionmentioning

confidence: 99%

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

Falguières

Maak

Weyhern

et al. 2008

Molecular Cancer Therapeutics

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The targeting of solid tumors requires delivery tools that resist intracellular and extracellular inactivation, and that are taken up specifically by tumor cells. We have shown previously that the recombinant nontoxic B-subunit of Shiga toxin (STxB) can serve as a delivery tool to target digestive tumors in animal models. The aim of this study was to expand these experiments to human colorectal cancer. Tissue samples of normal colon, benign adenomas, colorectal carcinomas, and liver metastases from 111 patients were obtained for the quantification of the expression of the cellular STxB receptor, the glycosphingolipid globotriaosyl ceramide (Gb 3 or CD77). We found that compared with normal tissue, the expression of Gb 3 was strongly increased in colorectal adenocarcinomas and their metastases, but not in benign adenomas. Short-term primary cultures were prepared from samples of 43 patients, and STxB uptake was studied by immunofluorescence microscopy. Of a given tumor sample, on average, 80% of the cells could visibly bind STxB, and upon incubation at 37°C, STxB was transported to the Golgi apparatus, following the retrograde route. This STxB-specific intracellular targeting allows the molecule to avoid recycling and degradation, and STxB could consequently be detected on tumor cells even 5 days after initial uptake. In conclusion, the targeting properties of STxB could be diverted for the delivery of contrast agents to human colorectal tumors and their metastases, whose early detection and specific targeting remains one of the principal challenges in oncology. [Mol Cancer Ther 2008;7(8):2498 -508]

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“…Therefore, different intracellular routing may play a pivotal role in cell susceptibility and triggering a different pathway for apoptosis. Stxinduced apoptosis and cytotoxicity are distinct processes (Gordon et al 2000;Williams et al 1999), although the A subunit can be necessary for apoptosis (Khine et al 2004). In our study, the same result was also shown, as if A subunit can separately induce apoptosis morphologically in higher concentration by Hoechst staining and DNA laddering method.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, it has been shown that apoptosis is involved in the Stx-mediated cytotoxicity of the renal tubular and lung epithelium cell lines (Uchida et al 1999). In this case, apoptosis was maintained at Stx concentrations, wherein protein synthesis inhibition was prevented; therefore, Stx-induced apoptosis and cytotoxicity are two distinct processes (Gordon et al 2000;Williams et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Study on induction of apoptosis on HeLa and Vero cells by recombinant shiga toxin and its subunits

2009

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Verotoxin (VT) or shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli (EHEC) and Shigella dysenteriae is AB5 holotoxin with potent protein synthesis inhibitor. VT can induce both apoptosis and necrosis depending on the cell type, it has been shown that VT-induced apoptosis and cytotoxicity are distinct processes, and the A subunit can be necessary for apoptosis. In other words, the precise role of each subunit in apoptosis signaling has yet to be established. In this study, induction of apoptosis has been examined by using both recombinant A and B subunits, and recombinant Stx (rStx) with different doses in HeLa and Vero cells. For this purpose, the polymyxin B extract of constructs expressing A, B and AB5 recombinant proteins was used. Therefore, amounts greater than normally reported were used to induce desire effects on cell lines. The apoptotic effect of A and B subunits appear at higher doses than that of rStx. The highest apoptotic effect was observed for rStx at low concentration, compared to A and B subunits. A or B subunits separately cannot induce the signaling pathway stimulated by holotoxin though A subunit, does induce laddering pattern similar to holotoxin. We concluded that both subunits are important in complete death signaling pathway. Since different concentration of A and B subunits and rStx was required in different assay, therefore, it could be emphasized that cell death or even apoptosis caused by either of the subunits or holotoxin depends on sensitivity or specificity of the assay and cell types used.

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CD40 ligand, Bcl-2, and Bcl-xL spare group I Burkitt lymphoma cells from CD77-directed killing via Verotoxin-1 B chain but fail to protect against the holotoxin

Cited by 33 publications

References 57 publications

Defensins from Insects and Plants Interact with Fungal Glucosylceramides

Defensins from Insects and Plants Interact with Fungal Glucosylceramides

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

Study on induction of apoptosis on HeLa and Vero cells by recombinant shiga toxin and its subunits

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