Correlation of abrin-mediated inhibition of protein synthesis and apoptosis

Tiwari, Vinita and Karande, Anjali A (2019) Correlation of abrin-mediated inhibition of protein synthesis and apoptosis. In: IUBMB LIFE, 71 (3). pp. 357-363.

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Abstract

The plant toxin, abrin, a type-II ribosome inactivating protein, is extremely lethal, the human fatal dose being similar to 1 mu g/kg body weight. Abrin has been classified as an agent for bioterrorism, which is of concern. Conversely, the high toxic property of abrin has been employed in generating immunotoxins, whereas its toxin moiety is conjugated to cell surface marker-specific antibodies for cell-targeted killing. Different cell types exhibit variable levels of sensitivity to abrin toxicity; therefore, adequate knowledge of the molecular mechanism that governs the activity of the protein would be a safeguard. To gain insights into this, two cell lines requiring strikingly different concentrations of abrin for inactivating ribosomes were studied. Employing conjugates of the wild-type and active site mutant of abrin A chain with the ricin B chain, it was found that abrin-induced apoptosis was dependent on inhibition of protein synthesis (PSI) leading to ER-stress in Ovcar-3 cells, but not in KB cells. Abrin was also observed to cause direct DNA damage in KB cells, while in Ovcar-3 cells abrin-induced DNA damage was found to be dependent on caspases. Overall, the study demonstrates that the correlation of abrin-mediated PSI and apoptosis is cell-specific and abrin can induce more than one pathway to cause cell death. (c) 2018 IUBMB Life, 71(3):357-363, 2019

Item Type:	Journal Article
Publication:	IUBMB LIFE
Publisher:	WILEY
Additional Information:	Copyright of this article belongs to WILEY
Keywords:	abrin; ribosome inactivating protein; abrin A chain; apoptosis; DNA damage
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	01 Mar 2019 05:33
Last Modified:	01 Mar 2019 05:33
URI:	http://eprints.iisc.ac.in/id/eprint/61870

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