TheCorynebacterium glutamicummycothiol peroxidase is a reactive oxygen species-scavenging enzyme that shows promiscuity in thiol redox control

2015 ◽  
Vol 96 (6) ◽  
pp. 1176-1191 ◽  
Author(s):  
Brandán Pedre ◽  
Inge Van Molle ◽  
Almudena F. Villadangos ◽  
Khadija Wahni ◽  
Didier Vertommen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Redox Control ◽  
Thiol Redox

scholarly journals Computational simulation of the reactive oxygen species and redox network in the regulation of chloroplast metabolism

2019 ◽  
Author(s):  
Melanie Gerken ◽  
Sergej Kakorin ◽  
Kamel Chibani ◽  
Karl-Josef Dietz
Keyword(s):  
Reactive Oxygen Species ◽  
Regulatory Network ◽  
Electron Flow ◽  
Computational Simulation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Animal Cells ◽  
Unknown Parameters ◽  
Target Proteins ◽  
Thiol Redox

AbstractCells contain a thiol redox regulatory network to coordinate metabolic and developmental activities with exogenous and endogenous cues. This network controls the redox state and activity of many target proteins. Electrons are fed into the network from metabolism and reach the target proteins via redox transmitters such as thioredoxin (TRX) and NADPH-dependent thioredoxin reductases (NTR). Electrons are drained from the network by reactive oxygen species (ROS) through thiol peroxidases, e.g., peroxiredoxins (PRX). Mathematical modeling promises access to quantitative understanding of the network function and was implemented for the photosynthesizing chloroplast by using published kinetic parameters combined with fitting to known biochemical data. Two networks were assembled, namely the ferredoxin (FDX), FDX-dependent TRX reductase (FTR), TRX, fructose-1,6-bisphosphatase pathway with 2-cysteine PRX/ROS as oxidant, and separately the FDX, FDX-dependent NADP reductase (FNR), NADPH, NTRC-pathway for 2-CysPRX reduction. Combining both modules allowed drawing several important conclusions of network performance. The resting H2O2 concentration was estimated to be about 30 nM in the chloroplast stroma. The electron flow to metabolism exceeds that into thiol regulation of FBPase more than 7000-fold under physiological conditions. The electron flow from NTRC to 2-CysPRX is about 5.46-times more efficient than that from TRX-f1 to 2-CysPRX. Under severe stress (30 μM H2O2) the ratio of electron flow to the thiol network relative to metabolism sinks to 1:251 whereas the ratio of electron flow from NTRC to 2-CysPRX and TRX-f1 to 2-CysPRX rises up to 1:80. Thus, the simulation provides clues on experimentally inaccessible parameters and describes the functional state of the chloroplast thiol regulatory network.Authors summaryThe state of the thiol redox regulatory network is a fundamental feature of all cells and determines metabolic and developmental processes. However, only some parameters are quantifiable in experiments. This paper establishes partial mathematical models which enable simulation of electron flows through the regulatory system. This in turn allows for estimating rates and states of components of the network and to tentatively address previously unknown parameters such as the resting hydrogen peroxide levels or the expenditure of reductive power for regulation relative to metabolism. The establishment of such models for simulating the performance and dynamics of the redox regulatory network is of significance not only for photosynthesis but also, e.g., in bacterial and animal cells exposed to environmental stress or pathological disorders.

scholarly journals Ebsulfur Is a Benzisothiazolone Cytocidal Inhibitor Targeting the Trypanothione Reductase of Trypanosoma brucei

2013 ◽  
Vol 288 (38) ◽  
pp. 27456-27468 ◽  
Author(s):  
Jun Lu ◽  
Suman K. Vodnala ◽  
Anna-Lena Gustavsson ◽  
Tomas N. Gustafsson ◽  
Birger Sjöberg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Trypanosoma Brucei ◽  
Mammalian Cells ◽  
Reactive Oxygen ◽  
Redox System ◽  
Trypanothione Reductase ◽  
Oxygen Species ◽  
African Trypanosomiasis ◽  
Thiol Redox

Trypanosoma brucei is the causing agent of African trypanosomiasis. These parasites possess a unique thiol redox system required for DNA synthesis and defense against oxidative stress. It includes trypanothione and trypanothione reductase (TryR) instead of the thioredoxin and glutaredoxin systems of mammalian hosts. Here, we show that the benzisothiazolone compound ebsulfur (EbS), a sulfur analogue of ebselen, is a potent inhibitor of T. brucei growth with a favorable selectivity index over mammalian cells. EbS inhibited the TryR activity and decreased non-protein thiol levels in cultured parasites. The inhibition of TryR by EbS was irreversible and NADPH-dependent. EbS formed a complex with TryR and caused oxidation and inactivation of the enzyme. EbS was more toxic for T. brucei than for Trypanosoma cruzi, probably due to lower levels of TryR and trypanothione in T. brucei. Furthermore, inhibition of TryR produced high intracellular reactive oxygen species. Hydrogen peroxide, known to be constitutively high in T. brucei, enhanced the EbS inhibition of TryR. The elevation of reactive oxygen species production in parasites caused by EbS induced a programmed cell death. Soluble EbS analogues were synthesized and cured T. brucei brucei infection in mice when used together with nifurtimox. Altogether, EbS and EbS analogues disrupt the trypanothione system, hampering the defense against oxidative stress. Thus, EbS is a promising lead for development of drugs against African trypanosomiasis.

Thiol redox control via thioredoxin and glutaredoxin systems

2005 ◽  
Vol 33 (6) ◽  
pp. 1375-1377 ◽  
Author(s):  
A. Holmgren ◽  
C. Johansson ◽  
C. Berndt ◽  
M.E. Lönn ◽  
C. Hudemann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Main Part ◽  
Current Knowledge ◽  
Control Mechanisms ◽  
Oxygen Species ◽  
Redox Control ◽  
Cellular Redox ◽  
Thiol Redox ◽  
Induced Apoptosis

The Trx (thioredoxin) and Grx (glutaredoxin) systems control cellular redox potential, keeping a reducing thiol-rich intracellular state, which on generation of reactive oxygen species signals through thiol redox control mechanisms. Here, we give a brief overview of the human Trx and Grx systems. The main part focuses on our current knowledge about mitochondrial Grx2, which facilitates mitochondrial redox homoeostasis during oxidative stress-induced apoptosis.

Mitochondria as a source of reactive oxygen species

2009 ◽  
pp. c3 ◽  
Author(s):  
Helena M. Cochemé ◽  
Michael P. Murphy
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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