Cell Lysis Induced by Ricin D and Ricin E in Various Cell Lines

Oda, Tatsuya; Komatsu, Nobukazu; Muramatsu, Tsuyoshi

doi:10.1271/bbb.61.291

Cited by 34 publications

(18 citation statements)

References 7 publications

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“…These ricin-mediated apoptotic events were caused at the concentration range at which protein synthesis was also severely inhibited. Although the relationship between the intoxication mechanism of ricin leading to the inhibition of protein synthesis and the apoptosis induction is still unclear, our previous study has demonstrated that ricin-mediated cell lysis was inhibited by BFA in BFAsensitive Vero cells, but not in BFA resistant MDCK cells (Oda et al, 1997). Regarding the effect of BFA on ricin cytotoxicity, it has been shown that, following receptormediated endocytosis, ricin molecules are found in the Golgi elements, and that protein synthesis inhibition by ricin is abolished by BFA, which affects the structure and functions of the Golgi apparatus without preventing the binding and subsequent internalization of ricin (Pelham, 1991;Yoshida et al, 1990;Yoshida et al, 1991).…”

Section: Discussionmentioning

confidence: 98%

Enhancement of Diphtheria Toxin-induced Apoptosis in Vero Cells by Combination Treatment with Brefeldin A and Okadaic Acid.

Kusano

Kageyama

Tamura

et al. 2001

Cell Struct. Funct.

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ABSTRACT. In the present study, we compared the abilities of ricin and diphtheria toxin to induce apoptosis in Vero cells. The cytolysis and DNA fragmentation by ricin paralleled its protein synthesis inhibitory activity. However, unlike ricin, diphtheria toxin could induce neither cytolysis nor DNA fragmentation in Vero cells up to very high concentration, in spite of the fact that Vero cells were even more sensitive to protein synthesis inhibition by diphtheria toxin than ricin. Interestingly, coexistence of brefeldin A (BFA) and okadaic acid (OA) significantly enhanced diphtheria toxin-mediated cytolysis and DNA fragmentation without affecting the activity of protein synthesis inhibition. Ammonium chloride almost completely abolished the ability of diphtheria toxin to induce apoptosis in the presence of BFA and OA as well as the protein synthesis inhibitory activity. The mutant CRM 197, which does not catalyze the ADP ribosylation of elongation factor-2 (EF-2), failed to induce apoptosis in Vero cells even in the presence of BFA and OA. Thus, translocation of diphtheria toxin into the cytosol and subsequent enzymatic inactivation of EF-2 may be necessary steps to induce apoptosis. Taken together our results suggest that protein synthesis inhibition by toxins is not sufficient to induce apoptosis, and underlying mechanisms of apoptosis induction may be distinct between ricin and diphtheria toxin. Since a morphological change in the Golgi complex was observed in Vero cells treated with BFA and OA, modulation of the Golgi complex by these reagents may be partly responsible for enhanced apoptosis induction by diphtheria toxin.

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Section: Discussionmentioning

confidence: 98%

Enhancement of Diphtheria Toxin-induced Apoptosis in Vero Cells by Combination Treatment with Brefeldin A and Okadaic Acid.

Kusano

Kageyama

Tamura

et al. 2001

Cell Struct. Funct.

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“…Precisely how type I RIPs which do not have a cell-binding chain inhibit fungi, i.e., how are they internalized, is not known. Both type I and type 2 RIPs show broad activity against a number of plant and human pathogenic fungi as well as toxicity against mammalian cells (some type 2 RIPs are highly toxic to animals, likely because of the presence of the cell-binding B chain) (132,142,146).…”

Section: Fungal Cell Wall Structurementioning

confidence: 99%

Antifungal Proteins

Selitrennikoff

2001

Appl Environ Microbiol

525

362

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“…Ricin was isolated from small castor beans as described by Mise et al (Mise et al, 1977 (Oda et al, 1997).…”

Section: Methodsmentioning

confidence: 99%

Butyric Acid Sensitizes Vero Cells to Ricin-Induced Apoptosis via Accelerated Activation of Multiple Signal Transduction Pathways

Tamura

Tsuruta

Hirano

et al. 2003

Cell Struct. Funct.

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ABSTRACT. We found that the treatment with 1 mM butyric acid for 2 days renders Vero cells highly sensitive to ricin-induced apoptosis reflected by cytolysis concomitant with apoptotic cellular and nuclear morphological changes, DNA fragmentation, and increase in caspase-3 like activity, whereas butyric acid alone had no cytotoxic effect on Vero cells. During the treatment with butyric acid, gradual increase in alkaline phosphatase activity, an indicator for butyric acid-induced differentiation, was observed in Vero cells. Although the potency of ricinmediated protein synthesis was increased in butyric acid-treated Vero cells as compared to untreated cells, the binding and internalization of ricin to the cells were not much affected. Furthermore, DNA fragmentation caused by other protein synthesis inhibitors such as diphtheria toxin and anisomysin were also highly potentiated in butyric acid-treated Vero cells, whereas the potencies of these toxins to inhibit the protein synthesis were not affected by butyric acid treatment. These results suggest that the apoptosis signaling pathway, which may be triggered by cytotoxic stress response caused by toxins, is sensitized in butyric acid-treated cells, while the pathways leading to the protein synthesis inhibition by these toxins are relatively unchanged. No significant differences in the expression levels of p21, p53, and Bcl-2 proteins were observed between butyric acid-treated and untreated Vero cells. The treatment with ricin resulted in the activation of p38 MAP kinase, and this activation occurred on an accelerated time schedule in butyric acid-treated Vero cells than in untreated cells. The specific inhibitor of p38 MAP kinase SB203580 showed a partial inhibitory effect on ricin-induced apoptosis in control Vero cells, but it was less effective in butyric acid-treated Vero cells. Taken together, our results suggest that butyric acid-treatment may result in sensitization of multiple intracellular signal transduction pathways including apoptotic signaling pathways and p38 MAP kinase pathway.Key words: ricin/butyric acid/apoptosis/differentiation/diphtheria toxin/anisomycin/p38 MAP kinase Ricin, a natural protein toxin present in castor bean (Ricinus communis), consists of two structurally and functionally different chains (A and B) which are linked together through a single disulfide bond. The A-chain is N-glycosidase which specifically cleaves the N-glycosidic bond of a single adenine residue in the 28S rRNA of 60S ribosomal subunit, and eventually inhibits cellular protein synthesis. The B-chain is a galactose or N-acetylgalactosamine specific lectin (Goldstein et al., 1985;Middlebrook and Dorland, 1984;Sandvig et al., 1989). The potent cytotoxicity of ricin is achieved by the collaboration of two chains. In addition to ricin, other protein toxins of plant (abrin and modeccin) and bacterial (diphtheria toxin, Pseudomonas toxin and Shiga toxin) origin, which belong to a group of toxins consisting of two moieties, inhibit cellular protein synthesis following rece...

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Cell Lysis Induced by Ricin D and Ricin E in Various Cell Lines

Cited by 34 publications

References 7 publications

Enhancement of Diphtheria Toxin-induced Apoptosis in Vero Cells by Combination Treatment with Brefeldin A and Okadaic Acid.

Enhancement of Diphtheria Toxin-induced Apoptosis in Vero Cells by Combination Treatment with Brefeldin A and Okadaic Acid.

Antifungal Proteins

Butyric Acid Sensitizes Vero Cells to Ricin-Induced Apoptosis via Accelerated Activation of Multiple Signal Transduction Pathways

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