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Институт теоретической и экспериментальной биофизики Российской академии наук.

ООО "ИЦ КОМКОН".




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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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«
Vol. 22, Art. 19 (pp. 271-292)    |    2021       
»

Molecular aspects of cytotoxicity of ricin
Chepur S.V., Al-Shekhadat R.I., Gogolevsky A.S., Pugach V.A.,
Myasnikov V.A., Anisenkova E.V., Levchuk E.V., Tyunin M.A.

State scientific-research test Institute of military medicine
of Defense Ministry of the Russian Federation

LLC «Innova plus»



Brief summary

On the ricin as an example by features of toxicity ribosome-inactivating proteins associated with their direct spatial oriented RNA-N-glycosidase activity that defines depurinization sarcin-ricin loop and blocking the hydrolysis of GTP with consequent impairment of translation in protein synthesis is characterized. Endocytosis of ricin and its transport through the Golgi complex determines the significant conformations of the toxin molecule necessary for its release in active form into the cytosol and binding to ribosomal structures. Complete or partial inhibition of ribosome function by ricin activates a cascade of proinflammatory reactions by inducing transcription factor NF-κB and mitogen-activated protein kinases signal pathways. The effect of ricin on Toll-like receptors mediates the production of cytokines, stimulating inflammatory responses. It was observed that the cytotoxic effect of ricin is also associated with the induction of mitochondria-mediated apoptosis. Due to its cytotoxic action, ricin can be used to develop new drugs for the treatment of cancer and autoimmune diseases. At the same time, retrograde transport blockers, substances which blocking intracellular ricin transport, anti-inflammatory drugs of various nature, and a number of antibacterial agents are considered as candidate agents that limit its toxic effect.


Key words

ricin, ribosomes, sarcin-ricin loop, apoptosis, induction of inflammation





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