Thionins toxicity

Figure 3 Comparison of several thionins reveals their structural similarity. The structures are color coded for their secondary structure, cyan a-helix, red /3-strand, magenta random coil/turn. (a) a-Purothionin (2plh) and (b) /3-purothionin (1 bhp) have four disulfide bonds, (c) Crambin (1 ejg) has three disulfide bonds. Despite its thionin fold it lacks antimicrobial or other toxic activity, (d) An overlay of crambin (1ejg, black), a-purothionin (2plh, red), /3-purothionin (1 bhp, orange), viscotoxin A3 (ledO, magenta), and viscotoxin B (Ijmp, cyan) from Viscum album reveals the conserved structure of the peptide backbone.

Bohimann H, Clausen S, Behnke S, Giese H. Hiller C, Rcimann-Philipp U, Schrader C, Batkholt V, Apel K. Leaf-specific thionins of barley—a novel class of cell wall proteins toxic to plant pathogenic fungi and possibly involved in the defence mechanism of plants. EMBO J 1988 7 1559-1565. 

When glutathione synthesis was inhibited by bu-thionine sulfoximine so that were was a 50 % depletion of glutathione, the immortalised rat mesencephalic cell line CSM14.1.4 showed an enhanced synergistic toxicity of sulphite and peroxynitrite (Marshall et al. 1999). Because sulphite is present normally in the brain as a product of cysteine metabolism, and because increased peroxynitrite formation has been reported in Parkinson s disease, these events might contribute to neuronal death. 

The first MFCs used a mediator, a chemical that transfers electrons from bacteria in the cell to the anode. Mediators include humic acid, methylene blue and thionine. Many mediators are toxic and expensive. In MFCs without mediators the bacteria have electron transfer proteins, such as cytochromes, on their outer membrane that can transfer electrons directly to the anode. 

A strikingly similar yet different peptide has been isolated from seeds of the crucifer Crambe abyssinica, and is called crambin (11). This peptide contains only three disulfide bonds, whose positions correspond to those of viscotoxin (12). It is very hydrophobic, is not positively charged as are the other thionins and consequently is not toxic. Because of its hydrophobic nature it is easy to crystallize, and the three dimensional structure has been determined by X-ray and neutron diffraction (13). Its three dimensional structure is very similar to that determined for the related thionin a 1 -purothionin, as discussed below (14,15). 

Because of their wide distribution in the plant world and the high degree of structure conservation, one would expect the thionins would play an important role in the economy of plant cells. The thionins isolated from seeds have been proposed to play a role as either a storage protein or as a toxin which protects the seed from insect, bacterial or fungal infestation. A role as a storage protein could better be performed by proteins which are not toxic, and this does not seem to be a major function of the thionins. It could be the role, however, for crambin which is non-toxic. 

The toxicity of the thionins is well documented for small animals, insects, bacteria, fungi and mammalian cells. It has been proposed that thionins could protect the starchy endosperm against the action of bacteria and fungi (16). A role as an inhibitor of DNA synthesis has been proposed for thionins, since purothionin inhibits ribonucleotide reductase when reduced thioredoxin served as the hydrogen donor (17). Other studies show that thionins affect cellular membrane permeability and inhibit growth as well as DNA, RNA and protein synthesis in mammalian cells (18). They are also hemolytic for human and animal erythrocytes (6). 

Gasanov, S. E., Vernon, L. P. and Aripov, T. F., 1992, Modification of phospholipid membrane structure by the plant toxic peptide pyrularia thionin. Arch. Biochem. Biophys., 30 367. 

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