Cell toxicity by ricin and elucidation of mechanism of Ricin inactivation

Souza, Lara C. Meneguelli De; Carvalho, Laís Pessanha de; Araújo, Jaciara Silva de; Melo, Édesio José Tenório de; Machado, Olga Lima Tavares

doi:10.1016/j.ijbiomac.2018.03.024

Cited by 22 publications

(13 citation statements)

References 26 publications

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“…Despite the very effective ricin-mediated rRNA depurination event that results in the inhibition of protein synthesis, it cannot be stated that these processes by themselves lead to cell death [24,30,31,32,33,203]. It has been demonstrated that ricin can induce apoptosis, autophagy and release of cytokine inflammatory mediators [25,26,27,28,29,30,204] (Figure 4).…”

Section: Cytotoxic Action Of Ricin On Cellsmentioning

confidence: 99%

Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin

Sowa-Rogozińska

Sominka

Nowakowska-Gołacka

et al. 2019

Toxins

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Ricin can be isolated from the seeds of the castor bean plant (Ricinus communis). It belongs to the ribosome-inactivating protein (RIP) family of toxins classified as a bio-threat agent due to its high toxicity, stability and availability. Ricin is a typical A-B toxin consisting of a single enzymatic A subunit (RTA) and a binding B subunit (RTB) joined by a single disulfide bond. RTA possesses an RNA N-glycosidase activity; it cleaves ribosomal RNA leading to the inhibition of protein synthesis. However, the mechanism of ricin-mediated cell death is quite complex, as a growing number of studies demonstrate that the inhibition of protein synthesis is not always correlated with long term ricin toxicity. To exert its cytotoxic effect, ricin A-chain has to be transported to the cytosol of the host cell. This translocation is preceded by endocytic uptake of the toxin and retrograde traffic through the trans-Golgi network (TGN) and the endoplasmic reticulum (ER). In this article, we describe intracellular trafficking of ricin with particular emphasis on host cell factors that facilitate this transport and contribute to ricin cytotoxicity in mammalian and yeast cells. The current understanding of the mechanisms of ricin-mediated cell death is discussed as well. We also comment on recent reports presenting medical applications for ricin and progress associated with the development of vaccines against this toxin.

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Section: Cytotoxic Action Of Ricin On Cellsmentioning

confidence: 99%

Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin

Sowa-Rogozińska

Sominka

Nowakowska-Gołacka

et al. 2019

Toxins

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“…34 , 44 The increased proteasome expression observed in the present study may thus act as a protective mechanism to prevent the aggregation of unfolded ricin A chain. 43 , 45…”

Section: Discussionmentioning

confidence: 99%

Effects of ricin on primary pulmonary alveolar macrophages

et al. 2019

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Objective We systematically investigated the cytotoxic effects of ricin in primary pulmonary alveolar macrophages (PAMs). Methods Primary PAMs were isolated from BALB/c mice. The cytotoxic effects of ricin were investigated in vitro by optical and transmission electron microscopy, detection of the inflammatory cytokine response, proteomic analysis, and subsequent biological functional analysis. Results Ricin induced shrinkage, apoptosis, vacuolization, and multi-organelle lesions in primary PAMs as demonstrated by optical and transmission electron microscopy. Ricin also induced a pronounced pro-inflammatory cytokine response in primary PAMs, including induction of tumor necrosis factor-α, interferon-γ, interleukin (IL)-1, IL-2, IL-6, IL-12, C-C motif chemokine ligand 2, and C-X-C motif chemokine ligand 2, while the anti-inflammatory cytokines IL-4 and IL-10 were less affected. Proteomic analysis and subsequent biological functional analysis identified eight proteins that were up/downregulated by ricin treatment and which might thus contribute to ricin toxicity. These proteins were involved in various functions, including redox, molecular chaperone, glycolysis, protein translation, and protein degradation functions. Conclusion The results of the present study further our understanding of the pathogenic mechanism of inhalational ricin poisoning.

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“…Ricin is a phytotoxin presented in seeds of Riccinus communis . It can be obtained both from the native seed as well as waste product obtained during extrusion of castor oil [69]. The castor plant grows wild in tropical and subtropical climates and the plant is cultivated in large scale for the commercial production of castor oil, a major component of the castor bean, with almost two million tons of seeds harvested annually.…”

Section: Introductionmentioning

confidence: 99%

“…The result is the inactivation of ribosomes in the cell and the blocking of protein synthesis, leading to cell death. A single ricin A chain is capable to inactivate approximately 1500 ribosomes per minute [69]. Toxicity results from the inhibition of protein synthesis, but other mechanisms are noted including apoptosis pathways, direct cell membrane damage, alteration of membrane structure and function, and release of cytokine inflammatory mediators [76].…”

Section: Introductionmentioning

confidence: 99%

Biological Toxins as the Potential Tools for Bioterrorism

Janik

Ceremuga

Saluk‐Bijak

et al. 2019

IJMS

115

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Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as “Chemicals produced by living organisms that have toxic properties for another organism”. Toxins are very attractive to terrorists for use in acts of bioterrorism. The first reason is that many biological toxins can be obtained very easily. Simple bacterial culturing systems and extraction equipment dedicated to plant toxins are cheap and easily available, and can even be constructed at home. Many toxins affect the nervous systems of mammals by interfering with the transmission of nerve impulses, which gives them their high potential in bioterrorist attacks. Others are responsible for blockage of main cellular metabolism, causing cellular death. Moreover, most toxins act very quickly and are lethal in low doses (LD50 < 25 mg/kg), which are very often lower than chemical warfare agents. For these reasons we decided to prepare this review paper which main aim is to present the high potential of biological toxins as factors of bioterrorism describing the general characteristics, mechanisms of action and treatment of most potent biological toxins. In this paper we focused on six most danger toxins: botulinum toxin, staphylococcal enterotoxins, Clostridium perfringens toxins, ricin, abrin and T-2 toxin. We hope that this paper will help in understanding the problem of availability and potential of biological toxins.

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Cell toxicity by ricin and elucidation of mechanism of Ricin inactivation

Cited by 22 publications

References 26 publications

Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin

Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin

Effects of ricin on primary pulmonary alveolar macrophages

Biological Toxins as the Potential Tools for Bioterrorism

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