Rapid peroxynitrite reduction by human peroxiredoxin 3: Implications for the fate of oxidants in mitochondria

Armas, María Inés De; Esteves, Romina; Viera, Nicolás; Reyes, Aníbal M.; Mastrogiovanni, Mauricio; Alegria, Thiago Gerônimo Pires; Netto, Luís Eduardo Soares; Tortora, Verónica; Radí, Rafael; Trujillo, Madia

doi:10.1016/j.freeradbiomed.2018.10.451

Cited by 48 publications

(34 citation statements)

References 109 publications

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“…PRX3 is primarily located in the mitochondria and plays crucial roles in the reduction and clearance of H 2 O 2 and peroxynitrite ( 26 ). Recent studies have demonstrated that PRX3 knockdown increases mitochondrial superoxide levels ( 48 ) and induces the activation of RAW264.7 macrophages ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Mammals have six PRXs, of which PRX3 is specifically localized in the mitochondria that is the main site for the formation of peroxynitrite and hydrogen peroxide. As the most abundant peroxidase in most mouse tissues, PRX3 not only eliminates a large amount of hydrogen peroxide but also functions as the main target of peroxynitrite in the mitochondria ( 25 , 26 ). Previous studies have shown that PRX3-knockout mice accumulate relatively high intracellular ROS levels, which increases the severity of LPS-induced lung injury ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

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Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

et al. 2021

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Pyroptosis is a newly discovered form of cell death. Peroxiredoxin 3 (PRX3) plays a crucial role in scavenging reactive oxygen species (ROS), but its hepatoprotective capacity in acetaminophen (APAP)-induced liver disease remains unclear. The aim of this study was to assess the role of PRX3 in the regulation of pyroptosis during APAP-mediated hepatotoxicity. We demonstrated that pyroptosis occurs in APAP-induced liver injury accompanied by intense oxidative stress and inflammation, and liver specific PRX3 silencing aggravated the initiation of pyroptosis and liver injury after APAP intervention. Notably, excessive mitochondrial ROS (mtROS) was observed to trigger pyroptosis by activating the NLRP3 inflammasome, which was ameliorated by Mito-TEMPO treatment, indicating that the anti-pyroptotic role of PRX3 relies on its powerful ability to regulate mtROS. Overall, PRX3 regulates NLRP3-dependent pyroptosis in APAP-induced liver injury by targeting mitochondrial oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

et al. 2021

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“…Assuming a diffusion-controlled rate for condensation, an apparent rate constants of ≥10 8 s −1 would be expected, considering the effective molarity and in the absence of steric hindrance. 170 The rate constants of resolution measured by us 64,126,170,171 and other groups 169,205 are much slower, in the range of 10 −1 −10 2 s −1 . As the resolution also includes the socalled fully folded (FF) to locally unfolded (LU) conformational transition, a slow FF to LU change would explain a slow resolution.…”

Section: Chemical Reviewsmentioning

confidence: 94%

“…127,139,140 Considering these facts, kinetics competition analyses have predicted that eukaryotic Prxs will be responsible for the reduction of most mitochondrial and cytoplasmic H 2 O 2 and peroxynitrite. 53,64,141,142 Accordingly, Prxs are considered key players protecting cells from oxidative stress.…”

Section: Peroxiredoxinsmentioning

confidence: 99%

Catalysis of Peroxide Reduction by Fast Reacting Protein Thiols

et al. 2019

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Life on Earth evolved in the presence of hydrogen peroxide, and other peroxides also emerged before and with the rise of aerobic metabolism. They were considered only as toxic byproducts for many years. Nowadays, peroxides are also regarded as metabolic products that play essential physiological cellular roles. Organisms have developed efficient mechanisms to metabolize peroxides, mostly based on two kinds of redox chemistry, catalases/peroxidases that depend on the heme prosthetic group to afford peroxide reduction and thiol-based peroxidases that support their redox activities on specialized fast reacting cysteine/selenocysteine (Cys/Sec) residues. Among the last group, glutathione peroxidases (GPxs) and peroxiredoxins (Prxs) are the most widespread and abundant families, and they are the leitmotif of this review. After presenting the properties and roles of different peroxides in biology, we discuss the chemical mechanisms of peroxide reduction by low molecular weight thiols, Prxs, GPxs, and other thiol-based peroxidases. Special attention is paid to the catalytic properties of Prxs and also to the importance and comparative outlook of the properties of Sec and its role in GPxs. To finish, we describe and discuss the current views on the activities of thiol-based peroxidases in peroxide-mediated redox signaling processes.

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“…It should be noted that detection of cellular oxidants requires competition with other pathways of their cellular elimination. For example, peroxiredoxins are assumed as major enzymatic scavengers of H 2 O 2 and ONOO − (Cox et al, 2009;Trujillo et al, 2017;De Armas et al, 2019;Zeida et al, 2019). Taking into account the estimated lifetime of both oxidants in the range of 0.3-1.6 ms both in the cytosolic and mitochondrial compartments (Trujillo et al, 2017), when present at 10 mM concentration, boronates would scavenge <0.001% (!)…”

Section: Subcellular Targeting Of Boronate Probesmentioning

confidence: 99%

Boronate-Based Probes for Biological Oxidants: A Novel Class of Molecular Tools for Redox Biology

et al. 2020

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Boronate-based molecular probes are emerging as one of the most effective tools for detection and quantitation of peroxynitrite and hydroperoxides. This review discusses the chemical reactivity of boronate compounds in the context of their use for detection of biological oxidants, and presents examples of the practical use of those probes in selected chemical, enzymatic, and biological systems. The particular reactivity of boronates toward nucleophilic oxidants makes them a distinct class of probes for redox biology studies. We focus on the recent progress in the design and application of boronate-based probes in redox studies and perspectives for further developments.

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Rapid peroxynitrite reduction by human peroxiredoxin 3: Implications for the fate of oxidants in mitochondria

Cited by 48 publications

References 109 publications

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

Catalysis of Peroxide Reduction by Fast Reacting Protein Thiols

Boronate-Based Probes for Biological Oxidants: A Novel Class of Molecular Tools for Redox Biology

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