Sandbox Reserved 1454

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This Sandbox is Reserved from Jan 22 through May 22, 2018 for use in the course Biochemistry II taught by Jason Telford at the Maryville University, St. Louis, Missouri, USA. This reservation includes Sandbox Reserved 1446 through Sandbox Reserved 1455.

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Abrin

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Introduction Abrus precatorius (or rosary peas) contain the protein abrin. Rosary peas are red and oval-shaped with a black edge towards one end. In some cultures, they are used to make beaded jewelry. Abrin can exhibit beneficial uses for medical research, but it can also be destructive if it directly enters an organism’s body because of its toxic properties. Structure Abrin is referred to as a type-2 ribosome-inactivating protein (RIP). The protein contains two chains: α and β which are connected by a disulfide bond. Both of the chains are water soluble. The water molecules hydrolyze the N-C glycosidic bond. The β chain allows the α chain to enter a cell because it attaches to the carbohydrate receptors. The β is composed of the following amino acids: Ile-Val-Glu-Lys-Ser-Lys-Ile-Ser-Ser-Ser-Arg-Tyr-Glu-Pro-Thr. The α chain is known as an N-glycosidase . Once the α chain is in a cell, the chain removes adenine bases and links to the 28S rRNA. The attachment causes the ribosome to be incompetent when trying to connect to an elongation factor leading to an inhibition of protein synthesis. Medical Potential Abrin has remained a key interest in a treatment for cancer. In one study, scientists wanted to see if abrin would decrease the number of colon cancer cells in vitro and vivo models. One experiment showed that purified abrin can influence cell cycle arrest and apoptosis. The study states abrin “significantly increased p21 mRNA expression and decreased PCNA, cyclin B1, Ki67 mRNA expression” which induced a halt in cell growth. For example, p21 can inhibit the CDK2 which regulates the checkpoints of the cell cycle; meaning, if there is an increased level of p21, more CDK2s will be affected. It also stated that abrin can enhance Bcl-2 which causes cytochrome c to be released. With this data, the study suggested that abrin could act as an anticancer treatment for colon cancer; however, a further experiment would have to test abrin’s impact on other cells such as erythrocytes, neurons, or dendritic cells. Negative Effects/Treatment If an entire rosary pea is ingested, the person will have mild to no symptoms. However, if the shell breaks, the effects of abrin will be released. Abrin is able to induce apoptosis and cell cycle arrest, ingestion of the protein abrin is lethal. If abrin is consumed or inhaled into the human system, symptoms will include difficulty breathing, vomiting, diarrhea, fever, and organ failure. The lethal dose of abrin is 0.1-1 micrograms Someone who has been poisoned by abrin will need fluids, a ventilator, and activated charcoal. Another method for suppressing the symptoms of abrin poisoning is to use CRRT and hemoperfusion. CRRT purifies the blood for a day’s duration. CRRT can destroy toxins up to 1-20kDa in size. Hemoperfusion, which is more effective than CRRT can filter the blood and cause a decrease in levels of the toxin. While these methods have the potential for successfully clearing a toxin, it is still essential for those that have been exposed to a toxin to seek medical help, fast and efficiently. Bioterrorism/Prevention Abrin is very similar to ricin because of its structure and functions. While abrin hasn’t been used for bioterrorism, there have been multiple occasions of ricin misuse. For example, in London of 1978, Georgi Markov was attacked by a man with an umbrella, who was employed by the Bulgarian secret service. The umbrella was designed to release a piece ricin which ended up lodging into Markov's skin. Markov died three days after being exposed to the toxin of ricin . Other acts of bioterrorism have included envelopes with the exposure to ricin being mailed to government officials including the President. Since then a vaccine has been created to suppress the effects of ricin poisoning. However, there is still a potential for the use of abrin in a bioterrorism attack. As of right now, they are in development of a vaccine and have learned in one study that a rATB vaccine will possibly rid the symptoms of abrin poisoning.

References

1. "Facts About Abrin.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 18 Nov. 2015, emergency.cdc.gov/agent/abrin/basics/facts.asp.