Isolated Ricin B-Chain-mediated Apoptosis in U937 Cells

IL-1 has (together with IL-6 and tumour necrosis factor) multiple effects in the systemic acute-phase response and in local acute and chronic inflammation: it stimulates T (helper) cells to synthesize IL-2 and IL-2 receptors, interferon gamma, and other lymphokines, B cells (proliferation and differentiation), neutrophils, and natural killer cells; stimulates monocytes and macrophages to produce IL-1, IL-6, and tumour necrosis factor; acts in the acute-phase response by inducing synthesis of acute-phase proteins in liver and reducing cytochrome P450 synthesis; induces natriuresis in kidney, insulin production in pancreas ß cells, muscular proteolysis ('easy' energy generation) in muscle cells, slow-wave sleep in cerebral cortex; raises the temperature set-point (fever) in hypothalamus; stimulates haematopoiesis and prostaglandin synthesis by various cell types (fibroblasts, macrophages, endothelium); inhibits gastric motility in vitro ; induces collagenase production by synovial cells and osteoclasts, and antiviral state; inhibits gastric smooth muscle in vitro ; is cytostatic for tumour cells and activates endothelium Interleukin 2.

26/04/2016 · Ricin Inhibition of in vitro Protein Synthesis by Plant Ribosomes: ..

Ricin is a 65-kDa glycoprotein toxin produced by theseeds of and has been classified as aribosome-inactivating protein (RIP) (). Ricin consists of a cytotoxic A chain(RTA) and a galactose-binding B chain (RTB) linked by a disulfidebond (). The A-chain is 32 kDa,targets the ribosome and inhibits protein synthesis in mammaliancells; the B-chain is 34 kDa and is a galactose-binding lectinprotein that binds to the eukaryotic cell membrane by interactingwith cell-surface molecules, such as galactose and glycolipids(,). RTB mediates ricin endocytosis andthe delivery of RTA to the cytosol of target cells, and RTB hasattracted attention due to its well-characterized endocytotictrafficking and efficacy over a wide range of cell types (,).Studies have shown that RTB can be successfully used as a carrierfused to other molecules. When RTB was fused to rotavirusnonstructural protein 4 (NSP4), the molecule stimulated a Th1lymphocyte response (). Inaddition, an RTB-GFP fusion protein expressed in tobacco has beenshown to generate humoral immune responses in immunized mice,indicating a Th2 response ().However, an understanding of the immune response induced by RTB isnecessary to determine the mechanisms by which RTB acts as animmunostimulant.


Protein Synthesis -Translation and Regulation

Ricin, a ribosome-inactivating protein from the seeds of the castor oil plant (Ricinus communis L.) is one of the most potent cell poisons known. It is able to bind and enter most mammalian cells where it exploits their fully reversible secretory pathway to reach the endoplasmic reticulum. Ricin is then able to exit the endoplasmic reticulum to access the cytosol where it inhibits protein synthesis, thus killing the cells. Castor bean ribosomes are sensitive to ricin, but the plant has developed strategies to protect its own cells from suicide. The intracellular routing of ricin has been traditionally studied by exogenously adding toxin to mammalian cells and by following its path through the cell. However, the extreme potency of this protein has prevented the final membrane transport step from being studied in detail. Now, the expression of ricin in heterologous plant cells is proving helpful in elucidating details of both toxin biosynthesis and vacuolar targeting, and in studying membrane translocation of the catalytic subunit from the endoplasmic reticulum to the cytosol.


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Ricin A-chain,which strongly inhibits protein synthesis by mammalian ribosomes,inhibited all of the plant ribosomal systems by 50% when present at25-45 μg/ml-≈23,000 times the concentration needed to inhibitmammalian systems.

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Ricinus communis agglutinin A-chain, a proteinsimilar to ricin A-chain, inhibited translation by the plant systems 50%at concentrations 5-10 times those of the ricin A-chain.

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Ricin, a ribosome-inactivating protein from the seeds of the castor oil plant (Ricinus communis L.) is one of the most potent cell poisons known. It is able to bind and enter most mammalian cells where it exploits their fully reversible secretory pathway to reach the endoplasmic reticulum. Ricin is then able to exit the endoplasmic reticulum to access the cytosol where it inhibits protein synthesis, thus killing the cells. Castor bean ribosomes are sensitive to ricin, but the plant has developed strategies to protect its own cells from suicide. The intracellular routing of ricin has been traditionally studied by exogenously adding toxin to mammalian cells and by following its path through the cell. However, the extreme potency of this protein has prevented the final membrane transport step from being studied in detail. Now, the expression of ricin in heterologous plant cells is proving helpful in elucidating details of both toxin biosynthesis and vacuolar targeting, and in studying membrane translocation of the catalytic subunit from the endoplasmic reticulum to the cytosol.

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Ribosomes fromcastor bean endosperm, the source of ricin and the agglutinin, were justas susceptible to the inhibitors as were ribosomes from the other fourplants.