Antioxidants Special Issue: Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family

Fisher, Aron B.

doi:10.3390/antiox8040107

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…PRDX6, as an antioxidant enzyme, could reduce cellular peroxides including short chain hydroperoxides and phospholipid hydroperoxides through its GPx activity, which could protect cells against oxidative stress [ 2 , 3 , 7 ]. There had been reported that inhibition or deficiency of PRDX6 could increase the intracellular oxidative stress and cause the cell injury [ [39] , [40] , [41] ].…”

Section: Discussionmentioning

confidence: 99%

“…The peroxiredoxins (PRDXs) are a ubiquitous family of highly conserved enzymes that use the thiol groups of their redox-active cysteines (Cys) to catalyze the reduction of peroxides, including hydrogen peroxide or other hydroperoxides [ [1] , [2] , [3] ]. The PRDXs are classified into two categories, 1-Cys and 2-Cys, based on whether the protein contains one or two conserved cysteine residues directly involved in catalysis [ [4] , [5] , [6] ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of peroxiredoxin 6 as a direct target of withangulatin A by quantitative chemical proteomics in non-small cell lung cancer

et al. 2021

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Peroxiredoxin 6 (PRDX6), as a bifunctional enzyme with glutathione peroxidase activity (GPx) and Ca2 + -independent phospholipase A2 (iPLA2) activity, has a higher expression in various cancer cells, which leads to the increase of antioxidant properties and promotes tumorigenesis. However, only a few inhibitors of PRDX6 have been discovered to date, especially the covalent inhibitors of PRDX6. Here, we firstly identified Withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PRDX6. SILAC-ABPP identified that WA could directly bind to PRDX6 and inactivate the enzyme activity of PRDX6 by the α, β-unsaturated ketone moiety. Moreover, WA also facilitated the generation of ROS, and inhibited the GPx and iPLA2 activities. However, WA-1, with a reduced α, β-unsaturated ketone moiety, had no significant inhibition of the GPx and iPLA2 activities. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selectively covalent binding of WA to the cysteine 47 residue (Cys47) of PRDX6, while mutation of Cys47 blocked the binding of WA to PRDX6. Notably, WA-mediated cytotoxicity and inhibition of the GPx and iPLA2 activities were almost abolished by the deficiency of PRDX6. Therefore, this study indicates that WA is a novel PRDX6 covalent inhibitor, which could covalently bind to the Cys47 of PRDX6 and holds great potential in developing anti-tumor agents for targeting PRDX6.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of peroxiredoxin 6 as a direct target of withangulatin A by quantitative chemical proteomics in non-small cell lung cancer

et al. 2021

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“…Prdx5 forms an intramolecular disulfide bond between the C P and C R, within one Prdx molecule and is returned to its reduced form though the action of Trx [ 65 ]. Prdx6 lacks the C R and is thus classified as a 1-Cys Prdx [ 66 , 67 ]. In contrast to the dependence of the reduction of Prdx1–5 on Trx, the disulfide bond in the oxidized form of Prdx6 is reduced by glutathione S-transferase π isoform (GSTπ) [ 68 ].…”

Section: Prdxsmentioning

confidence: 99%

The Role of Peroxiredoxins in the Regulation of Sepsis

2022

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Oxidative stress, a result of a disturbance in redox homeostasis, is considered to be one of the main aggravating events in the pathogenesis of immune disorders. Peroxiredoxins (Prdxs) are an enzyme family that catalyzes the reduction of peroxides, including hydrogen peroxide, lipid peroxides, and nitrogen peroxides. Although the maintenance of cellular redox homeostasis through Prdxs is essential for surviving in adverse environments, Prdxs also participate in the regulation of cellular signal transduction by modulating the activities of a panel of molecules involved in the signal transduction process. Although Prdxs were discovered as intracellular anti-oxidative enzymes, recent research has revealed that Prdxs also play important roles in the extracellular milieu. Indeed, Prdxs have been shown to have the capacity to activate immune cells through ligation with innate immune receptors such as toll-like receptors (TLRs). In this review, we will summarize the intracellular as well as extracellular roles of Prdxs for and against the pathogenesis of inflammatory disorders including sepsis, hemorrhagic shock, and drug-induced liver injury.

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“…Glutathione peroxidase (GPx) and peroxiredoxins (PRX) correspond to the most efficient peroxidases from the cellular point of view and in according to the literature mammals exhibit six PRX groups, in addition to expanding the PRX1 group into four closely related subgroups (PRX1-4) plus PRX5 and PRX6 [18][19][20][21][22]. Moreover, these enzymes utilize GSH and GSH S-transferase (GST) for reduction and resolution of their oxidized peroxidative cysteines (Cys) [23,24].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Thiol-dependent Enzymes on the Pharmacological Effects Induced by the Catalytically Active PLA2 from Bothrops jararacussu

Toyama¹,

Crc²,

Mn³

et al. 2021

Preprint

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Background: Clinical cases reports with snake accidents show that venom bite induces increased oxidative stress including several markers of lipid peroxidation and other oxidative stress marker in plasma. Methods: The main findings of this work were performed with BthTx-II on paw edema of animals treated with the toxin and biochemical measurement of COX-2, PGE2, MDA and the effects of peroxiredoxin inhibitors on edema and myotoxicity were also evaluated. Results: The results show that edema and myotoxocity induced by PLA2 (BthTx-II) induces a strong mobilization of arachidonic acid and an increase in cellular oxidative stress as measured by increased malondialdehydo (MDA) concentration and protein carbonylation. Thus, these findings establish the strong link between oxidative stress, arachidonic acid mobilization and that these events may explain the presence of oxidative stress markers in snake-bitten patients. Experiments performed with animals previously treated with commercially purchased inhibitors showed enzymes such as thioredoxin (TXN), thioredoxin reductase (TXNRD) and other glutathione (GSH)-related antioxidant defenses could play an essential role controlling and defining the end of edema on the late phase of PLA2 BthTx-II-induced process. Conclusion. This study showed that thioate-dependent antioxidant enzymes play an important role in resolving the edema induced by BthTx-II.

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Antioxidants Special Issue: Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family

Abstract: The peroxiredoxins, first discovered about 30 years ago, are the most recently described family of ubiquitously expressed antioxidant enzymes [...]

Cited by 14 publications

References 35 publications

Identification of peroxiredoxin 6 as a direct target of withangulatin A by quantitative chemical proteomics in non-small cell lung cancer

Identification of peroxiredoxin 6 as a direct target of withangulatin A by quantitative chemical proteomics in non-small cell lung cancer

The Role of Peroxiredoxins in the Regulation of Sepsis

Evaluation of Thiol-dependent Enzymes on the Pharmacological Effects Induced by the Catalytically Active PLA2 from Bothrops jararacussu

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