Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of neurotransmitter release by tetanus toxin and botulinum neurotoxin A can be mimicked by intracellular application of the corresponding toxin light chains. The aim of this study was to determine whether the two-chain toxins are reduced by brain preparations to yield free light chains which would represent the ultimate toxins. The interchain disulfide of two-chain tetanus toxin was cleaved by rat cortex homogenate fortified with NADPH. Reduction was promoted further by addition of thioredoxin. Thioredoxin reductase was demonstrated in and purified from porcine brain cortex. The thioredoxin system which consisted of purified enzyme, thioredoxin and NADPH reduced both toxins. The resulting light chains appeared homogeneous in SDS gel electrophoresis. The complementary heavy chain of tetanus but not of botulinum toxin migrated in two bands, the faster one with the velocity of heavy chain obtained by chemical reduction. The major, slower form was converted into the faster by chemical but not by enzymatic reduction. Tetanus toxin, whether in its single-chain or two-chain version also occurred in two forms which differed by their electrophoretic mobility. The two forms of single-chain toxin were interconverted by chemical reduction or oxidation but not by the thioredoxin system. It is concluded that a) a thioredoxin system in brain tissue reduces the interchain disulfide of two-chain tetanus toxin and botulinum neurotoxin A, b) tetanus toxin but not botulinum neurotoxin A consists of two electrophoretically distinct forms which differ by the thiol-disulfide status of their heavy chains, c) the disulfide loop within the heavy chain of tetanus toxin is resistant to the thioredoxin system.
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PMID:Reductive cleavage of tetanus toxin and botulinum neurotoxin A by the thioredoxin system from brain. Evidence for two redox isomers of tetanus toxin. 157 25

This study tested the hypothesis that reactive oxygen intermediates present in unfatigued skeletal muscle act to enhance contractile function. Fiber bundles from rat diaphragm were incubated with exogenous catalase (an antioxidant enzyme that dehydrates hydrogen peroxide to molecular oxygen and water) to decrease the tissue concentration of reactive oxygen intermediates. Catalase (10(3) U/ml) significantly decreased twitch characteristics (time to peak tension, half-relaxation time, peak force, and twitch-to-tetanus force ratio), thereby shifting the force-frequency relationship to the right. Catalase effects were dose dependent. Concentrations of 1 to 10(5) U/ml progressively depressed submaximal (30-Hz) tetanic stress, whereas concentrations > 10(5) U/ml were toxic, inhibiting maximal (200-Hz) tetanic stress (P < 0.0001). Exogenous hydrogen peroxide (10(-4) to 10(-2)M) increased peak twitch stress (P < 0.03) and lengthened both time to peak tension (P < 0.02) and half-relaxation time (P < 0.02). Selective removal of superoxide anion radicals with the use of superoxide dismutase produced dose-dependent contractile inhibition similar to that produced by catalase. We conclude that the reactive oxygen intermediates present in unfatigued skeletal muscle have a positive effect on excitation-contraction coupling and are obligatory for optimal contractile function.
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PMID:Reactive oxygen in skeletal muscle. III. Contractility of unfatigued muscle. 822 15

Botulinum and tetanus neurotoxins are the most toxic substances known and form the growing family of clostridial neurotoxins. They are composed of a metalloprotease light chain (L), linked via a disulfide bond to a heavy chain (H). H mediates the binding to nerve terminals and the membrane translocation of L into the cytosol where their substrates, the three SNARE proteins, are localised. L translocation is accompanied by unfolding, and it has to be reduced and reacquire the native fold to exert its neurotoxicity. The Thioredoxin reductase-Thioredoxin system is responsible for the reduction, but it is unknown whether the refolding of L is spontaneous or aided by host chaperones. Here we report that geldanamycin, a specific inhibitor of heat shock protein 90, hampers the refolding of L after membrane translocation and completely prevents the cleavage of SNAREs. We also found that geldanamycin strongly synergises with PX-12, an inhibitor of thioredoxin, suggesting that the processes of L chain refolding and interchain disulfide reduction are strictly coupled. Indeed we found that the heat shock protein 90 and the Thioredoxin reductase-Thioredoxin system physically interact on synaptic vesicle where they orchestrate a chaperone-redox machinery which is exploited by clostridial neurotoxins to deliver their catalytic part into the cytosol.
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PMID:Hsp90 is involved in the entry of clostridial neurotoxins into the cytosol of nerve terminals. 2740 98