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Publication Detail

Title: Brevetoxin-2, is a unique inhibitor of the C-terminal redox center of mammalian thioredoxin reductase-1.

Authors: Chen, Wei; Tuladhar, Anupama; Rolle, Shantelle; Lai, Yanhao; Rodriguez Del Rey, Freddy; Zavala, Cristian E; Liu, Yuan; Rein, Kathleen S

Published In Toxicol Appl Pharmacol, (2017 08 15)

Abstract: Karenia brevis, the Florida red tide dinoflagellate produces a suite of neurotoxins known as the brevetoxins. The most abundant of the brevetoxins PbTx-2, was found to inhibit the thioredoxin-thioredoxin reductase system, whereas the PbTx-3 has no effect on this system. On the other hand, PbTx-2 activates the reduction of small disulfides such as 5,5'-dithio-bis-(2-nitrobenzoic acid) by thioredoxin reductase. PbTx-2 has an α, β-unsaturated aldehyde moiety which functions as an efficient electrophile and selenocysteine conjugates are readily formed. PbTx-2 blocks the inhibition of TrxR by the inhibitor curcumin, whereas curcumin blocks PbTx-2 activation of TrxR. It is proposed that the mechanism of inhibition of thioredoxin reduction is via the formation of a Michael adduct between selenocysteine and the α, β-unsaturated aldehyde moiety of PbTx-2. PbTx-2 had no effect on the rates of reactions catalyzed by related enzymes such as glutathione reductase, glutathione peroxidase or glutaredoxin.

PubMed ID: 28551108 Exiting the NIEHS site

MeSH Terms: Animals; Cell Line; Cell Survival/drug effects; Curcumin/pharmacology; Dose-Response Relationship, Drug; Enzyme Inhibitors/toxicity*; Humans; Lipid Peroxidation/drug effects; Marine Toxins/toxicity*; Oxidation-Reduction; Oxocins/toxicity*; Protein Domains; Rats; Selenocysteine; Thioredoxin Reductase 1/antagonists & inhibitors*; Thioredoxin Reductase 1/chemistry; Thioredoxin Reductase 1/metabolism; Time Factors

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