Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/25/2012
Publication Date: 6/25/2012
Citation: Rasooly, R., He, X., Friedman, M. 2012. Milk inhibits the biological activity of ricin. Journal of Biological Chemistry. 287(33):27924-27929. doi:10.1074/jbc.M112.362988. Interpretive Summary: Ricin has already been proven to be an effective bioterrorism agent. There is interest in identifying and designing effective inhibitors of ricin, to counteract this bioterrorism threat. Previous studies indicate that ricin toxicity can be inhibited by synthetic compounds. Because synthetic compounds might not be safe to consume or be food-compatible, the objective of our studies is to explore the potential of foods and their bioactive constituents to inhibit biological activity of ricin. In the present study, we show that commercial fat-free milk has this potential.
Technical Abstract: Ricin is a highly toxic protein produced by the castor plant Ricinus communis. The toxin is relatively easy to isolate and can be used as a biological weapon. There is great interest in identifying effective inhibitors for ricin. In this study, we demonstrated by three independent assays that component of reconstituted powdered milk has a high binding affinity to ricin. We discovered that milk can competitively bind to and reduces the amount of toxin available to asialofetuin type II, which is used as a model to study the binding of ricin to galactose cell-surface receptors. Milk also removes ricin bound to the microtiter plate. In parallel experiments, we demonstrated by activity assay and by immuno-PCR (IPCR) that milk can competitively bind to ricin, reducing the amount of toxin uptake by the cells and thus inhibit ricin’s biological activity. The inhibitory effect of milk on ricin activity in Vero cells was at the same level as by anti-ricin antibodies. We also found that milk did not inhibit the activity of another ribosome inactivating protein, Shiga toxin type 2(Stx2), produced by pathogenic Escherichia coli O157:H7. Unlike ricin, which is internalized into the cells via a galactose-binding site, Stx2 is internalized through the cell surface receptor glycolipid globotriasylceramide (Gb3 and Gb4). These observations suggest that ricin toxicity may possibly be reduced by a widely consumed natural liquid food.