The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins.

Endo, Yaeta; Mitsui, Kazuhiro; Motizuki, Mitsuyoshi; Tsurugi, Kunio

doi:10.1016/s0021-9258(18)45660-8

Cited by 1,103 publications

(150 citation statements)

References 22 publications

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“…2 RTA is a ribosomeinactivating protein (RIP) that catalyzes the hydrolysis of a conserved residue within the sarcin/ricin loop of 28S rRNA. [3][4][5] Ricin, which is mannosylated at three different positions, is also very efficiently taken up by cells that express the mannose receptor (MR; CD206), such as Kupffer cells (KCs) and alveolar macrophages (AM). 6 Ultimately, ricin-intoxicated cells undergo programmed cell death.…”

Section: Introductionmentioning

confidence: 99%

An intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation

Rong

Torres-Vélez

Ehrbar

et al. 2019

Human Vaccines & Immunotherapeutics

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Ricin toxin, a plant-derived, mannosylated glycoprotein, elicits an incapacitating and potentially lethal inflammatory response in the airways following inhalation. Uptake of ricin by alveolar macrophages (AM) and other pulmonary cell types occurs via two parallel pathways: one mediated by ricin's B subunit (RTB), a galactosespecific lectin, and one mediated by the mannose receptor (MR;CD206). Ricin's A subunit (RTA) is a ribosomeinactivating protein that triggers apoptosis in mammalian cells. It was recently reported that a single monoclonal antibody (MAb), PB10, directed against an immunodominant epitope on RTA and administered intravenously, was able to rescue Rhesus macaques from lethal aerosol dose of ricin. In this study, we now demonstrate in mice that the effectiveness PB10 is significantly improved when combined with a second MAb, SylH3, against RTB. Mice treated with PB10 alone survived lethal-dose intranasal ricin challenge, but experienced significant weight loss, moderate pulmonary inflammation (e.g., elevated IL-1 and IL-6 levels, PMN influx), and apoptosis of lung macrophages. In contrast, mice treated with the PB10/SylH3 cocktail were essentially impervious to pulmonary ricin toxin exposure, as evidenced by no weight loss, no change in local IL-1 and IL-6 levels, retention of lung macrophages, and a significant dampening of PMN recruitment into the bronchoalveolar lavage (BAL) fluids. The PB10/SylH3 cocktail only marginally reduced ricin binding to target cells in the BAL, suggesting that the antibody mixture neutralizes ricin by interfering with one or more steps in the RTB-and MR-dependent uptake pathways.

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Section: Introductionmentioning

confidence: 99%

An intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation

Rong

Torres-Vélez

Ehrbar

et al. 2019

Human Vaccines & Immunotherapeutics

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“…CUS, which has a variety of biological activities such as anti-virus, anti-fertility and anti-tumor, prevents elongation factors from binding to ribosomes to inhibit protein biosynthesis at the protein level [7]. After intervention of CUS, apoptotic was observed by electron microscope and apoptotic peak was also observed by ow cytometry in PANC-1RG7 cells obviously, which was consistent with the previous research results that CUS could induce apoptosis of pancreatic cancer cells [4,[8][9][10].…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine-Resistance Reversion of Cucurmosin in Human Pancreatic Cancer Cells

Wang

Fu²,

Huang

et al. 2021

Preprint

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Objective To investigate the effects of cucurmosin (CUS) on proliferation and drugs resistance in gemcitabine (GEM) human pancreatic cancer cell PANC-1RG7. Methods The ultrastructural changes of PANC-1RG7 cells after CUS intervention were observed by transmission electron microscope. Flow Cytometer (FCM) was used to detect the effect of CUS on the growth cycle of PANC-1RG7 cells. We used colony formation experiment, Sulforhodamine B assays and subcutaneous implantation tumor model to observe the proliferation inhibition and reversal drug-resistance reversion of CUS on PANC-1RG7 in vitro and in vivo. Western blot was used to observe the expressions of RRM1, RRM2, PI3K, Akt, mTOR and other proteins related to apoptosis after CUS intervention. Results After CUS intervention, PANC-1RG7 cells were obviously apoptotic with large number of vacuoles and apoptotic bodies. Compared with parental cell PANC-1, GEM-resistant cell PANC-1 was more sensitive to CUS. The combination of GEM and CUS at different concentrations showed synergistic effect. At the concentration of CUS with the inhibition rate of 10%, the reversal multiples and the reversal efficiency were 1.78±0.65 and 50.13±16.87%, respectively. Subcutaneous implantation tumor model confirmed the proliferation inhibitory effect of CUS in vitro. Western blot confirmed that CUS down-regulated the expressions of RRM1, RRM2, PI3K, Akt and mTOR. Conclusion CUS can significantly inhibit PANC-1RG7 cell proliferation in vivo and in vitro, and can reverse cell GEM-resistance.

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“…Ricin CS , a mutated Ricin A chain, inactivates eukaryotic ribosomes by hydrolytically cleaving the N-glycosidic bond (A4324) of the 28S ribosomal RNA subunit at high temperatures (30°C), but not at low temperatures (18°C) (Endo et al, 1987; Endo and Tsurugi, 1987; Moffat et al, 1992; Allen et al, 2002). We previously validated the spatiotemporal effect of Ricin CS inhibition in the Drosophila brain using lateral clock neurons.…”

Section: Methodsmentioning

confidence: 99%

CREB repressor in mushroom body enhances Drosophila LTM formation

Chen

Feng

et al. 2021

Preprint

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Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information, however, becomes permanent memory. How the brain gates relevant information into LTM remains unclear. In Drosophila adults, a single training session in an olfactory aversive task is not sufficient to induce protein synthesis-dependent LTM. Instead, multiple spaced training sessions are required. Here, we report that initial learning induces neural activity in the early α/β subset of Kenyon cells of the mushroom body (MB), and output from these neurons inhibits LTM formation. Specifically in response to spaced training, Schnurri activates CREBB expression which then appears to suppress the inhibitory output from MB. One training session can enhance LTM formation when this inhibitory effect is relieved. We propose that learning-induced protein synthesis and spaced training-induced CREBB act antagonistically to modulate output from early α/β MB neurons during LTM formation.

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The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins.

Cited by 1,103 publications

References 22 publications

An intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation

An intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation

Gemcitabine-Resistance Reversion of Cucurmosin in Human Pancreatic Cancer Cells

CREB repressor in mushroom body enhances Drosophila LTM formation

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