Protein synthesis inhibition ricin/abrin

Abrin exerts its toxic action in the same way as ricin. The abrin B-chain avidly binds to a variety of cell types, in particular reticuloendothehal cells which bear the appropriate mannose receptors. The abrin B-chain also binds to the galactosyl-terminated receptors on the cell membrane to allow the entry of the abrin A-chain. Once internalized, the abrin A-chain is transported from the cell membrane to the ribosomes, where it catalytically inactivates the 60S ribosomal subunit by removing adenine from positions 4 and 324 of 28S rRNA, thereby inhibiting protein synthesis and causing cell death (Stripe and Barbieri, 1986). 

Viscum contain lectins that are cytotoxic by inhibiting protein synthesis on the ribosomal level in a manner similar to the toxalbumins ricin and abrin. Viscotoxin and phoratoxin are cardiac toxins and vasoconstrictors. Both produced reflex bradycardia, negative inotropic effects, and, in high doses, vasoconstriction of skin and skeletal muscle vessels in animals. 

Shiga toxin produced by Shigella dysenteriae has similar structural features. The toxin binds to a glycolipid (Gb3), undergoes endocytosis, and the enzymatie Ai fragment, which is a specific N-glycosidase, removes adenine from one particular adenosine residue in the 28S RNA of the 60S ribosomal subunit. Removal of the adenine inactivates the 60S ribosome, blocking protein synthesis. Ricin, abrin, and a number of related plant proteins inhibit eukaryotic protein synthesis in a similar manner (Chapter 25). 

A group of plant lectins, such as abrin, ricin, and mod-eccin, are highly toxic to eukaryotic cells. Their mode of action consists of inhibition of protein synthesis by enzymatically inactivating the EF-2 binding region of the 60S ribosomal subunit, whereas the diphtheria toxin inactivates the EF-2 protein itself. Ricin is isolated from castor beans and has a molecular weight of 66,000. Like most plant and bacterial toxic proteins, ricin contains two... 

After addition of ricin, abrin, or modeccin to cell culture medium in vitro, there is a characteristic time delay before the inhibition of protein synthesis becomes apparent the lag time decreases with increasing toxin concentration, but even at high concentrations it is as long as 20-30 min (Refsnes et al., 1974 Olsnes et al., 1976). The cause of this time delay is unknown, but it may partly reflect the complex intracellular trafficking of the toxins. 

Olsnes, S., Sandvig, K., Refsnes, K. and Pihl, A. (1976) Rates of different steps involved in the inhibition of protein synthesis by the toxic lectins abrin and ricin. J Biol Chem, 251, 3985-3992. 

Toxin derived from the seeds of the Rosary pea or Jequirity bean (Abrus pecatorius). Powdered abrin is yellowish-white it is soluble in water and stable. Two glycoprotein chains acidic chain (30000D) - inhibits protein synthesis neutral chain (35 000D) - binds to cell wall and facilitates entry. Effects similar to ricin qv, but it is more toxic. 

ML-1. Lectin found in mistletoe. Comparable in toxicity with ricin and abrin inhibits protein synthesis as does ricin. 

The binding, entry, and action of ricin, abrin, and modeccin on eukaryotic cellular systems have been reviewed.Modeccin binds to surface receptors containing terminal D-galactosyl residues, and like abrin and ricin it inhibits protein synthesis by inactivating the 60 S ribosomal sub-units. Competition experiments with various glycoproteins have indicated that the modeccin receptors are different from abrin receptors. Mutant cell lines resistant to abrin and ricin were not resistant to modeccin and vice-versa. 

Plant Ricin Abrin Both inhibit protein synthesis... 

Abrin, a potent toxin, is extracted from the seeds of the rosary pea (Abrus precatorius). Due to its easy availability and preparation, this toxin is an attractive option for weap-onizing in poor countries, and thus has also been included in the Sch ule 1 of the CWC. The mechanism of action of abrin is very similar to that of ricin however, in mice, abrin is 75 times more toxic than that of ricin (0.04 pg/ kg for abrin is equivalent to 3pg/kg of ricin). Similar to ricin, inhalation of abrin is found to be more toxic than ingestion. However, abrin ingestion has reported to be toxic to the liver, unlike ricin. At the cellular level, abrin is a potent toxalbumin known to cause cell death by inhibiting protein synthesis (namely, type 2 ribosomal inhibitory protein). Further, abrin is also known to induce endothelial cell damage leading to an increase in cell permeability, fluid and protein leakage, and tissue edema. 

Symptoms are secondary to the inhibition of protein synthesis and cell death. Death is usually due to multi-organ failure. Ingested in larger doses, abrin causes severe diarrhoea and victims can die of subsequent shock. The symptoms of abrin exposure are the much the same as ricin, and are summarised in Table 5.25 (p. 314). 

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