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1.
Christopher Horst Lillig Carsten Berndt Arne Holmgren 《Biochimica et Biophysica Acta (BBA)/General Subjects》2008
Glutaredoxins utilize the reducing power of glutathione to maintain and regulate the cellular redox state and redox-dependent signaling pathways, for instance, by catalyzing reversible protein S-glutathionylation. Due to the general importance of these processes, glutaredoxins have been implied in various physiological and disease-related conditions, such as immune defense, cardiac hypertrophy, hypoxia-reoxygenation insult, neurodegeneration and cancer development, progression as well as treatment. The past years have seen an impressive gain of knowledge regarding new glutaredoxin systems and functions. This is true both with respect to new functions in redox regulation and also with respect to unexpected new ties to iron metabolism and iron–sulfur cluster biosynthesis. The aim of this review is to provide a state-of-the-art overview over these recent discoveries with a focus on aspects related to human health. 相似文献
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Oxidative stress is a major common hallmark of many neurodegenerative disease such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and stroke. Novel concepts in our understanding of oxidative stress indicate that a perturbed redox circuitry could be strongly linked with the onset of such diseases. In this respect, glutathione and thioredoxin dependent antioxidant enzymes play a central role as key regulators due to the fact that a slight dysfunction of any of these enzymes leads to sustained reactive oxygen species (ROS) production. Apart from their classical role as ROS scavengers, some of these enzymes are also able to control post-translational modifications. Therefore, efficient control of ROS production and reversibility of post-translational modifications are critical as improper control of such events may lead to the activation of pathological redox circuits that eventually culminate in neuronal cell death. To dissect the apparently opposing functions of ROS in cell physiology and pathophysiology, a proper working toolkit is mandatory. In vivo modeling is an absolute requirement due to the complexity of redox signaling systems that often contradict data obtained from in vitro approaches. Hence, inducible/conditional knockout mouse models for key redox enzymes are emerging as powerful tools to perturb redox circuitries in a temporal and spatial manner. In this review we address the basics of ROS generation, chemistry and detoxification as well as examples in where applications of mouse models of important enzymes have been successfully applied in the study of neurodegenerative processes. We also highlight the importance of new models to overcome present technical limitations in order to advance in the study of redox processes in the role of neurodegeneration. 相似文献
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The active site in the [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki F has been investigated by Fourier transform infrared (FTIR) spectroscopy. Analysis of the spectra allowed the three diatomic inorganic ligands to Fe in this enzyme to be identified as one CO molecule and two CN(-) molecules. Furthermore, pH-dependent redox titrations were performed to determine the midpoint potentials as well as the pK value of the respective reactions and revealed that each single-electron redox transition is accompanied by a single-proton transfer step. The comparison of these spectra with those published for other [NiFe] hydrogenases shows that the electronic structure of the active sites of these enzymes and their redox processes are essentially the same. Nevertheless, differences with respect to the frequency of the CO band and the pH dependence of the Ni-R states have been observed. Finally, the frequency shifts of the bands in the IR spectra were interpreted with respect to the electronic configuration of the redox intermediates in the catalytic cycle. 相似文献
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Biological systems rely on heme-proteins to carry out a number of basic functions essential for their survival. Hemes, or iron-porphyrin complexes, are the versatile and ubiquitous active centers of these proteins. In the past decade, discovery of new heme-proteins, together with functional and structural research, provided a wealth of information on these diverse and biologically important molecules. Structure determination work has shown that nature has used a variety of different scaffolds and architectures to bind heme and modulate functions such as redox properties. Structural data have also provided insights into the heme-linked protein conformational changes required in many regulatory heme-proteins. Remarkable efforts have been made towards the understanding of factors governing redox potentials. Site-directed mutagenesis studies and theoretical calculations on heme environments investigated the roles of hydrophobic and electrostatic residues, and analyzed the effect of heme solvent accessibility. This review focuses on the structure-function relationships underlying the association of heme in signaling and iron metabolism proteins. In addition, an account is given about molecular features affecting heme's redox properties; this briefly revisits previous conclusions in the light of some more recent reports. 相似文献
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By its ability to engage in a variety of redox reactions and coordinating metals, cysteine serves as a key residue in mediating enzymatic catalysis, protein oxidative folding and trafficking, and redox signaling. The thiol redox system, which consists of the glutathione and thioredoxin pathways, uses the cysteine residue to catalyze thiol-disulfide exchange reactions, thereby controlling the redox state of cytoplasmic cysteine residues and regulating the biological functions it subserves. Here, we consider the thiol redox systems of Escherichia coli and Saccharomyces cerevisiae, emphasizing the role of genetic approaches in the understanding of the cellular functions of these systems. We show that although prokaryotic and eukaryotic systems have a similar architecture, they profoundly differ in their overall cellular functions. 相似文献
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Yano T 《Molecular aspects of medicine》2002,23(5):345-368
The energy-transducing NADH: quinone (Q) oxidoreductase (complex I) is the largest and most complicated enzyme complex in the oxidative phosphorylation system. Complex I is a redox pump that uses the redox energy to translocate H(+) (or Na(+)) ions across the membrane, resulting in a significant contribution to energy production. The need to elucidate the molecular mechanisms of complex I has greatly increased. Many devastating neurodegenerative disorders have been associated with complex I deficiency. The structural and functional complexities of complex I have already been established. However, intricate biogenesis and activity regulation functions of complex I have just been identified. Based upon these recent developments, it is apparent that complex I research is entering a new era. The advancement of our knowledge of the molecular mechanism of complex I will not only surface from bioenergetics, but also from many other fields as well, including medicine. This review summarizes the current status of our understanding of complex I and sheds light on new theories and the future direction of complex I studies. 相似文献
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Reduction of the endoplasmic reticulum accompanies the oxidative damage of diabetes mellitus 总被引:4,自引:0,他引:4
The endoplasmic reticulum (ER), similary to other subcompartments of the eukaryotic cell possesses a relatively oxidizing environment. The special milieu of ER lumen is important for many ER-specific processes (redox protein folding, glycoprotein synthesis, quality control of secreted proteins, antigen presentation, etc.). Despite of the vital importance of redox regulation in the ER, we have a surprisingly fragmented knowledge about the mechanisms responsible for the ER redox balance. Moreover, new observations on disulfide bridge synthesis and on glutathione functions urge us to revise our recent theories based on many indirect and in vitro results. We have also very little information about the effects of different pathological conditions on the thiol metabolism and redox folding in the ER. Examining the role of molecular chaperones in the cellular pathology of diabetes mellitus we found that the ER redox environment shifted to a more reducing state, which was followed by changes of the thiol metabolism and structural-functional changes of the protein machinery involved in the redox folding process in diabetes. The possible consequences of these unexpected changes are also discussed. 相似文献
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《Critical reviews in biochemistry and molecular biology》2013,48(2):173-181
AbstractRapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol–disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol–disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities. 相似文献
9.
Trehalose-derived glasses are shown to support long range electron transfer reactions between spatially well separated donors and protein acceptors. The results indicate that these matrices can be used not only to greatly stabilize protein structures but also to facilitate both thermal and photo-initiated hemeprotein reduction over large macroscopic distances. To date the promise of exciting new protein-based technologies that can harness the exceptional tunability of protein functionality has been significantly thwarted by both intrinsic instability and stringent solvent/environment requirements for the expression of functional properties. The presented results raise the prospect of overcoming these limitations with respect to incorporating redox active proteins into solid state devices such as tunable batteries, switches, and solar cells. The findings also have implications for formulations intended to enhance long term storage of biomaterials, new protein-based synthetic strategies, and biophysical studies of functional intermediates trapped under nonequilibrium conditions. In addition, the study shows that certain sugars such as glucose or tagatose, when added to redox-inactive glassy matrices, can be used as a source of thermal electrons that can be harvested by suitable redox active proteins, raising the prospect of using common sugars as an electron source in solid state thermal fuel cells. 相似文献
10.
Plants are redox systems and redox-active compounds control and regulate all aspects of their life. Recent studies have shown that changes in reactive oxygen species (ROS) concentration mediated by enzymatic and non-enzymatic antioxidants are transferred into redox signals used by plants to activate various physiological responses. An overview of the main antioxidants and redox signaling in plant cells is presented. In this review, the biological effects of ROS and related redox signals are discussed in the context of acclimation to changing environmental conditions. Special attention is paid to the role of thiol/disulfide exchange via thioredoxins (Trxs), glutaredoxins (Grxs) and peroxiredoxins (Prxs) in the redox regulatory network. In plants, chloroplasts and mitochondria occupying a chloroplasts and mitochondria play key roles in cellular metabolism as well as in redox regulation and signaling. The integrated redox functions of these organelles are discussed with emphasis on the importance of the chloroplast and mitochondrion to the nucleus retrograde signaling in acclimatory and stress response. 相似文献
11.
Upon electrolytic reduction of a range of nitro-aromatic complexes (including imidazoles. benzenoids. furans and pyrazoles) an associated oxidation-reduction process is observed at more positive potentials with respect to nitro group reduction when using repeat scan cyclic voltammetry. This new couple has been identified as the reversible first reduction of the nitroso derivative for chloramphenicol, by the addition of a genuine sample of nitrosochloramphenicol to the electrochemical cell. We have failed to observe formation of the new redox-active species for five 5-nitroimidazoles examined.
Possible reaction schemes for nitroso formation under electrolytic reduction conditions and the importance of the nitroso redox couple with respect to the cytotoxic action of the parent drug are discussed. The applicability of nitrosochloramphenicol as a model for the behaviour of nitroso-heterocycles in general is shown. 相似文献
Possible reaction schemes for nitroso formation under electrolytic reduction conditions and the importance of the nitroso redox couple with respect to the cytotoxic action of the parent drug are discussed. The applicability of nitrosochloramphenicol as a model for the behaviour of nitroso-heterocycles in general is shown. 相似文献
12.
《Free radical research》2013,47(6):327-332
Upon electrolytic reduction of a range of nitro-aromatic complexes (including imidazoles. benzenoids. furans and pyrazoles) an associated oxidation-reduction process is observed at more positive potentials with respect to nitro group reduction when using repeat scan cyclic voltammetry. This new couple has been identified as the reversible first reduction of the nitroso derivative for chloramphenicol, by the addition of a genuine sample of nitrosochloramphenicol to the electrochemical cell. We have failed to observe formation of the new redox-active species for five 5–nitroimidazoles examined.Possible reaction schemes for nitroso formation under electrolytic reduction conditions and the importance of the nitroso redox couple with respect to the cytotoxic action of the parent drug are discussed. The applicability of nitrosochloramphenicol as a model for the behaviour of nitroso-heterocycles in general is shown. 相似文献
13.
Quinoproteins: structure, function, and biotechnological applications 总被引:13,自引:0,他引:13
A new class of oxidoreductase containing an amino acid-derived o-quinone cofactor, of which the most typical is pyrroloquinoline quinone (PQQ), is called quinoproteins, and has been recognized as the third redox enzyme following pyridine nucleotide- and flavin-dependent dehydrogenases. Some quinoproteins include a heme c moiety in addition to the quinone cofactor in the molecule and are called quinohemoproteins. PQQ-containing quinoproteins and quinohemoproteins have a common structural basis, in which PQQ is deeply embedded in the center of the unique superbarrel structure. Increased evidence for the structure and function of quinoproteins has revealed their unique position within the redox enzymes with respect to catalytic and electron transfer properties, and also to physiological and energetic function. The peculiarities of the quinoproteins, together with their unique substrate specificity, have encouraged their biotechnological application in the fields of biosensing and bioconversion of useful compounds, and also to environmental treatment. 相似文献
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Dardalhon M Kumar C Iraqui I Vernis L Kienda G Banach-Latapy A He T Chanet R Faye G Outten CE Huang ME 《Free radical biology & medicine》2012,52(11-12):2254-2265
Intracellular redox homeostasis is crucial for many cellular functions but accurate measurements of cellular compartment-specific redox states remain technically challenging. To better characterize redox control in the nucleus, we targeted a yellow fluorescent protein-based redox sensor (rxYFP) to the nucleus of the yeast Saccharomyces cerevisiae. Parallel analyses of the redox state of nucleus-rxYFP and cytosol-rxYFP allowed us to monitor distinctively dynamic glutathione (GSH) redox changes within these two compartments under a given condition. We observed that the nuclear GSH redox environment is highly reducing and similar to the cytosol under steady-state conditions. Furthermore, these sensors are able to detect redox variations specific for their respective compartments in glutathione reductase (Glr1) and thioredoxin pathway (Trr1, Trx1, Trx2) mutants that have altered subcellular redox environments. Our mutant redox data provide in vivo evidence that glutathione and the thioredoxin redox systems have distinct but overlapping functions in controlling subcellular redox environments. We also monitored the dynamic response of nucleus-rxYFP and cytosol-rxYFP to GSH depletion and to exogenous low and high doses of H2O2 bursts. These observations indicate a rapid and almost simultaneous oxidation of both nucleus-rxYFP and cytosol-rxYFP, highlighting the robustness of the rxYFP sensors in measuring real-time compartmental redox changes. Taken together, our data suggest that the highly reduced yeast nuclear and cytosolic redox states are maintained independently to some extent and under distinct but subtle redox regulation. Nucleus- and cytosol-rxYFP register compartment-specific localized redox fluctuations that may involve exchange of reduced and/or oxidized glutathione between these two compartments. Finally, we confirmed that GSH depletion has profound effects on mitochondrial genome stability but little effect on nuclear genome stability, thereby emphasizing that the critical requirement for GSH during growth is linked to a mitochondria-dependent process. 相似文献
16.
Michelet L Zaffagnini M Massot V Keryer E Vanacker H Miginiac-Maslow M Issakidis-Bourguet E Lemaire SD 《Photosynthesis research》2006,89(2-3):225-245
Oxidants are widely considered as toxic molecules that cells have to scavenge and detoxify efficiently and continuously. However, emerging evidence suggests that these oxidants can play an important role in redox signaling, mainly through a set of reversible post-translational modifications of thiol residues on proteins. The most studied redox system in photosynthetic organisms is the thioredoxin (TRX) system, involved in the regulation of a growing number of target proteins via thiol/disulfide exchanges. In addition, recent studies suggest that glutaredoxins (GRX) could also play an important role in redox signaling especially by regulating protein glutathionylation, a post-translational modification whose importance begins to be recognized in mammals while much less is known in photosynthetic organisms. This review focuses on oxidants and redox signaling with particular emphasis on recent developments in the study of functions, regulation mechanisms and targets of TRX, GRX and glutathionylation. This review will also present the complex emerging interplay between these three components of redox-signaling networks.Electronic Supplementary Material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
17.
The variety of cellular functions performed by proteins of the thioredoxin superfamily is made possible by the wide range of redox potential associated with their active site -Cys-X-X-Cys- motif. The determinants of these differences in redox potential are of considerable interest but are not well understood. E. coli Glutaredoxin 1 (Grx1) and 3 (Grx3) are important model systems with different redox properties, despite sharing the same -Cys-Pro-Tyr-Cys- motif, very similar overall structures, and 33% sequence identity. Very long molecular dynamics simulations (0.25 micros total) and electrostatic calculations provide a revised view of the reduced Grx1 active site, which now can be reconciled with biochemical and functional data. Comparison of this new model to Grx3 uncovers differences in the structure, dynamics, and electrostatics of these active sites. The influence of peripheral residues on the properties of the -Cys-X-X-Cys- motif is illustrated specifically with the effect of a Lys to Arg substitution. 相似文献
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Pierre Pétriacq Linda de Bont Guillaume Tcherkez Bertrand Gakière 《Plant signaling & behavior》2013,8(1)
Many metabolic processes that occur in living cells involve oxido-reduction (redox) chemistry underpinned by redox compounds such as glutathione, ascorbate and/or pyridine nucleotides. Among these redox carriers, nicotinamide adenine dinucleotide (NAD) is the cornerstone of cellular oxidations along catabolism and is therefore essential for plant growth and development. In addition to its redox role, there is now compelling evidence that NAD is a signal molecule controlling crucial functions like primary and secondary carbon metabolism. Recent studies using integrative -omics approaches combined with molecular pathology have shown that manipulating NAD biosynthesis and recycling lead to an alteration of metabolites pools and developmental processes, and changes in the resistance to various pathogens. NAD levels should now be viewed as a potential target to improve tolerance to biotic stress and crop improvement. In this paper, we review the current knowledge on the key role of NAD (and its metabolism) in plant responses to pathogen infections. 相似文献