Correlation of abrin-mediated inhibition of protein synthesis and apoptosis.
The plant toxin, abrin, a type-II ribosome inactivating protein, is extremely lethal, the human fatal dose being ~1 μg/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. © 2018 IUBMB Life, 71(3):357-363, 2019.
['Tiwari|Vinita|V|', 'Karande|Anjali A|AA|0000-0003-1251-7085']
D000036:Abrin D017209:Apoptosis D045744:Cell Line, Tumor D004249:DNA Damage D004305:Dose-Response Relationship, Drug D059865:Endoplasmic Reticulum Stress D006001:Glycoconjugates D006367:HeLa Cells D006801:Humans D009154:Mutation D009928:Organ Specificity D014176:Protein Biosynthesis D011994:Recombinant Proteins D012270:Ribosomes D012276:Ricin D013329:Structure-Activity Relationship
apoptosis abrin ribosome inactivating protein abrin A chain DNA damage