Effectors of thioredoxin reductase: Brevetoxins and manumycin-A.
Animals
Gene Expression Regulation, Enzymologic
/ drug effects
Humans
Insecta
Mammals
Marine Toxins
/ chemistry
NADPH Oxidases
/ metabolism
Oxocins
/ chemistry
Polyenes
/ chemistry
Polyunsaturated Alkamides
/ chemistry
Species Specificity
Thioredoxin-Disulfide Reductase
/ metabolism
Thioredoxins
/ metabolism
Algal toxin
Oxidative stress
Reactive oxygen species
Thioredoxin reductase
Journal
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
ISSN: 1532-0456
Titre abrégé: Comp Biochem Physiol C Toxicol Pharmacol
Pays: United States
ID NLM: 100959500
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
20
11
2018
accepted:
21
11
2018
pubmed:
27
11
2018
medline:
26
2
2019
entrez:
27
11
2018
Statut:
ppublish
Résumé
The activities of two effectors, brevetoxin (PbTx) and manumycin-A (Man-A), of thioredoxin reductase (TrxR) have been evaluated against a series of fourteen TrxR orthologs originating from mammals, insects and protists and several mutants. Man-A, a molecule with numerous electrophilic sites, forms a covalent adduct with most selenocystine (Sec)-containing TrxR enzymes. The evidence also demonstrates that Man-A can form covalent adducts with some non-Sec-containing enzymes. The activities of TrxR enzymes towards various substrates are moderated by Man-A either positively or negatively depending on the enzyme. In general, the reduction of substrates by Sec-containing TrxR is inhibited and NADPH oxidase activity is activated. For non-Sec-containing TrxR the effect of Man-A on the reduction of substrates is variable, but NADPH oxidase activity can be activated even in the absence of covalent modification of TrxR. The effect of PbTx is less pronounced. A smaller subset of enzymes is affected by PbTx. With a single exception, the activities of most of this subset are activated. Although both PbTx variants can react with selenocysteine, a stable covalent adduct is not formed with any of the TrxR enzymes. The key findings from this work are (i) the identification of an alternate mechanism of toxicity for the algal toxin brevetoxin (ii) the demonstration that covalent modification of TrxR is not a prerequisite for the activation of NADPH oxidase activity of TrxR and (iii) the identification of an inhibitor which can discriminate between cytosolic and mitochondrial TrxR.
Identifiants
pubmed: 30476593
pii: S1532-0456(18)30271-0
doi: 10.1016/j.cbpc.2018.11.015
pmc: PMC7485175
mid: NIHMS1516214
pii:
doi:
Substances chimiques
Marine Toxins
0
Oxocins
0
Polyenes
0
Polyunsaturated Alkamides
0
brevetoxin 2
0
brevetoxin 3
0
Thioredoxins
52500-60-4
NADPH Oxidases
EC 1.6.3.-
Thioredoxin-Disulfide Reductase
EC 1.8.1.9
manumycin
OIQ298X4XD
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
76-86Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM094172
Pays : United States
Organisme : NIEHS NIH HHS
ID : S11 ES011181
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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