The N-terminal cysteine is a dual sensor of oxygen and oxidative stress

2021 ◽  
Vol 118 (50) ◽  
pp. e2107993118
Author(s):  
Ah Jung Heo ◽  
Su Bin Kim ◽  
Chang Hoon Ji ◽  
Dohyun Han ◽  
Su Jin Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Regulatory Proteins ◽  
Oxygen Species ◽  
Cellular Homeostasis ◽  
Sequestosome 1 ◽  
Ros Homeostasis ◽  
Dual Sensor ◽  
And Oxidative Stress

Cellular homeostasis requires the sensing of and adaptation to intracellular oxygen (O2) and reactive oxygen species (ROS). The Arg/N-degron pathway targets proteins that bear destabilizing N-terminal residues for degradation by the proteasome or via autophagy. Under normoxic conditions, the N-terminal Cys (Nt-Cys) residues of specific substrates can be oxidized by dioxygenases such as plant cysteine oxidases and cysteamine (2-aminoethanethiol) dioxygenases and arginylated by ATE1 R-transferases to generate Arg-CysO2(H) (R-CO2). Proteins bearing the R-CO2 N-degron are targeted via Lys48 (K48)–linked ubiquitylation by UBR1/UBR2 N-recognins for proteasomal degradation. During acute hypoxia, such proteins are partially stabilized, owing to decreased Nt-Cys oxidation. Here, we show that if hypoxia is prolonged, the Nt-Cys of regulatory proteins can be chemically oxidized by ROS to generate Arg-CysO3(H) (R-CO3), a lysosomal N-degron. The resulting R-CO3 is bound by KCMF1, a N-recognin that induces K63-linked ubiquitylation, followed by K27-linked ubiquitylation by the noncanonical N-recognin UBR4. Autophagic targeting of Cys/N-degron substrates is mediated by the autophagic N-recognin p62/SQTSM-1/Sequestosome-1 through recognition of K27/K63-linked ubiquitin (Ub) chains. This Cys/N-degron–dependent reprogramming in the proteolytic flux is important for cellular homeostasis under both chronic hypoxia and oxidative stress. A small-compound ligand of p62 is cytoprotective under oxidative stress through its ability to accelerate proteolytic flux of K27/K63-ubiquitylated Cys/N-degron substrates. Our results suggest that the Nt-Cys of conditional Cys/N-degron substrates acts as an acceptor of O2 to maintain both O2 and ROS homeostasis and modulates half-lives of substrates through either the proteasome or lysosome by reprogramming of their Ub codes.

Differential susceptibility of a few members of the nasuta–albomicans complex of Drosophila to paraquat-induced lethality and oxidative stress

Genome ◽  
2011 ◽  
Vol 54 (10) ◽  
pp. 829-835 ◽  
Author(s):  
Mysore S. Ranjini ◽  
Ravikumar Hosamani ◽  
Muralidhara ◽  
Nallur B. Ramachandra
Keyword(s):  
Oxidative Stress ◽  
Biochemical Analysis ◽  
Reduced Glutathione ◽  
Differential Susceptibility ◽  
Activity Levels ◽  
Oxygen Species ◽  
Stress Markers ◽  
The Status ◽  
Markers Of Oxidative Stress ◽  
And Oxidative Stress

The evolution of karyotypically stabilized short-lived (SL) and long-lived (LL) cytoraces in the laboratory have been established and validated through our previous lifespan studies. In the present investigation, we examined the possible reason(s) for the differential longevity among selected members of SL and LL cytoraces, employing the well known paraquat (PQ) resistance bioassay. Exposure of these races to varying concentrations of PQ revealed relatively higher resistance among LL cytoraces than SL cytoraces, as evident by the lower incidence of mortality. Biochemical analysis for endogenous markers of oxidative stress revealed that LL-2 cytorace exhibited lower reactive oxygen species (ROS) and lipid peroxidation (LPO) levels, higher activity levels of superoxide dismutase (SOD), and coupled with higher levels of reduced glutathione (GSH) compared with the levels found in SL-2 cytorace. These findings suggest that the higher susceptibility of SL cytoraces to PQ challenge may be, at least in part, related to the higher endogenous levels of oxidative stress markers. Although the precise mechanisms responsible for the longer longevity among LL cytoraces of the nasuta–albomicans complex of Drosophila merits further investigation, our data suggest that the relatively longer lifespan may be related to the status of endogenous markers that renders them more resistant towards oxidative-stress-mediated lethality, as evident in the PQ assay.

scholarly journals Oxidative Stress Inside the Pathogenesis of Ascending Aorta Aneurysms: A Clearer Vision for Identifying Promising Biomarkers and Therapeutic Targets

2021 ◽  
Author(s):  
Carmela Balistreri ◽  
Calogera Pisano ◽  
Giovanni Ruvolo
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Genetic Variants ◽  
Complex Disease ◽  
Ascending Aorta ◽  
Oxygen Species ◽  
Aorta Aneurysm ◽  
Independent Risk Factors ◽  
The Impact ◽  
And Oxidative Stress

Ascending aorta aneurysm (AsAA) is a complex disease, currently defined an inflammatory disease. In the sporadic form, AsAA has, indeed, a complex physiopathology with a strong inflammatory basis, significantly modulated by genetic variants in innate/inflammatory genes, acting as independent risk factors and as largely evidenced in our recent studies performed during the last 10 years. Based on these premises, here, we want to revise the impact of reactive oxygen species (ROS) and oxidative stress on AsAA pathophysiology and consequently on the onset and progression of sporadic AsAA. This might consent to add other important pieces in the intricate puzzle of the pathophysiology of this disease with the translational aim to identify biomarkers and targets to apply in the complex management of AsAA, by facilitating the AsAA diagnosis currently based only on imaging evaluations, and the treatment exclusively founded on surgery approaches.

scholarly journals Advanced Glycation End Products and Oxidative Stress in a Hyperglycaemic Environment

2021 ◽  
Author(s):  
Akio Nakamura ◽  
Ritsuko Kawahrada
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Advanced Glycation End Products ◽  
Reactive Oxygen ◽  
Protein Glycation ◽  
Oxygen Species ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

Protein glycation is the random, nonenzymatic reaction of sugar and protein induced by diabetes and ageing; this process is quite different from glycosylation mediated by the enzymatic reactions catalysed by glycosyltransferases. Schiff bases form advanced glycation end products (AGEs) via intermediates, such as Amadori compounds. Although these AGEs form various molecular species, only a few of their structures have been determined. AGEs bind to different AGE receptors on the cell membrane and transmit signals to the cell. Signal transduction via the receptor of AGEs produces reactive oxygen species in cells, and oxidative stress is responsible for the onset of diabetic complications. This chapter introduces the molecular mechanisms of disease onset due to oxidative stress, including reactive oxygen species, caused by AGEs generated by protein glycation in a hyperglycaemic environment.

scholarly journals The Role of MicroRNAs in Diabetes-Related Oxidative Stress

2019 ◽  
Vol 20 (21) ◽  
pp. 5423 ◽  
Author(s):  
Mirza Muhammad Fahd Qadir ◽  
Dagmar Klein ◽  
Silvia Álvarez-Cubela ◽  
Juan Domínguez-Bendala ◽  
Ricardo Luis Pastori
Keyword(s):  
Oxidative Stress ◽  
Target Gene ◽  
Cellular Stress ◽  
Cellular Damage ◽  
Oxygen Species ◽  
Non Coding Rnas ◽  
And Oxidative Stress

Cellular stress, combined with dysfunctional, inadequate mitochondrial phosphorylation, produces an excessive amount of reactive oxygen species (ROS) and an increased level of ROS in cells, which leads to oxidation and subsequent cellular damage. Because of its cell damaging action, an association between anomalous ROS production and disease such as Type 1 (T1D) and Type 2 (T2D) diabetes, as well as their complications, has been well established. However, there is a lack of understanding about genome-driven responses to ROS-mediated cellular stress. Over the last decade, multiple studies have suggested a link between oxidative stress and microRNAs (miRNAs). The miRNAs are small non-coding RNAs that mostly suppress expression of the target gene by interaction with its 3’untranslated region (3′UTR). In this paper, we review the recent progress in the field, focusing on the association between miRNAs and oxidative stress during the progression of diabetes.

Underlying mechanisms of reactive oxygen species and oxidative stress photoinduced by graphene and its surface-functionalized derivatives

2020 ◽  
Vol 7 (3) ◽  
pp. 782-792 ◽  
Author(s):  
Hongye Yao ◽  
Yang Huang ◽  
Xuan Li ◽  
Xuehua Li ◽  
Hongbin Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Functional Groups ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Underlying Mechanisms ◽  
Transformation Processes ◽  
And Oxidative Stress

Graphene can be modified by different functional groups through various transformation processes in the environment.

scholarly journals β-Lapachone Induces Acute Oxidative Stress in Rat Primary Astrocyte Cultures that is Terminated by the NQO1-Inhibitor Dicoumarol

2020 ◽  
Vol 45 (10) ◽  
pp. 2442-2455
Author(s):  
Johann Steinmeier ◽  
Sophie Kube ◽  
Gabriele Karger ◽  
Eric Ehrke ◽  
Ralf Dringen
Keyword(s):  
Oxidative Stress ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Glutathione Disulfide ◽  
Cellular Accumulation ◽  
Primary Astrocyte ◽  
Cultured Astrocytes ◽  
Rat Astrocytes ◽  
Quinone Acceptor ◽  
And Oxidative Stress

Abstract β-lapachone (β-lap) is reduced in tumor cells by the enzyme NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1) to a labile hydroquinone which spontaneously reoxidises to β-lap, thereby generating reactive oxygen species (ROS) and oxidative stress. To test for the consequences of an acute exposure of brain cells to β-lap, cultured primary rat astrocytes were incubated with β-lap for up to 4 h. The presence of β-lap in concentrations of up to 10 µM had no detectable adverse consequences, while higher concentrations of β-lap compromised the cell viability and the metabolism of astrocytes in a concentration- and time-dependent manner with half-maximal effects observed for around 15 µM β-lap after a 4 h incubation. Exposure of astrocytes to β-lap caused already within 5 min a severe increase in the cellular production of ROS as well as a rapid oxidation of glutathione (GSH) to glutathione disulfide (GSSG). The transient cellular accumulation of GSSG was followed by GSSG export. The β-lap-induced ROS production and GSSG accumulation were completely prevented in the presence of the NQO1 inhibitor dicoumarol. In addition, application of dicoumarol to β-lap-exposed astrocytes caused rapid regeneration of the normal high cellular GSH to GSSG ratio. These results demonstrate that application of β-lap to cultured astrocytes causes acute oxidative stress that depends on the activity of NQO1. The sequential application of β-lap and dicoumarol to rapidly induce and terminate oxidative stress, respectively, is a suitable experimental paradigm to study consequences of a defined period of acute oxidative stress in NQO1-expressing cells.

scholarly journals Redox Regulation and Oxidative Stress: The Particular Case of the Stallion Spermatozoa

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 567 ◽  
Author(s):  
Fernando J. Peña ◽  
Cristian O’Flaherty ◽  
José M. Ortiz Rodríguez ◽  
Francisco E. Martín Cano ◽  
Gemma L. Gaitskell-Phillips ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Redox Regulation ◽  
Redox Homeostasis ◽  
Reactive Oxygen ◽  
Mitochondrial Activity ◽  
Oxygen Species ◽  
Redox Biology ◽  
Major Interest ◽  
And Oxidative Stress

Redox regulation and oxidative stress have become areas of major interest in spermatology. Alteration of redox homeostasis is recognized as a significant cause of male factor infertility and is behind the damage that spermatozoa experience after freezing and thawing or conservation in a liquid state. While for a long time, oxidative stress was just considered an overproduction of reactive oxygen species, nowadays it is considered as a consequence of redox deregulation. Many essential aspects of spermatozoa functionality are redox regulated, with reversible oxidation of thiols in cysteine residues of key proteins acting as an “on–off” switch controlling sperm function. However, if deregulation occurs, these residues may experience irreversible oxidation and oxidative stress, leading to malfunction and ultimately death of the spermatozoa. Stallion spermatozoa are “professional producers” of reactive oxygen species due to their intense mitochondrial activity, and thus sophisticated systems to control redox homeostasis are also characteristic of the spermatozoa in the horse. As a result, and combined with the fact that embryos can easily be collected in this species, horses are a good model for the study of redox biology in the spermatozoa and its impact on the embryo.

scholarly journals Prenatal Hypoxia and Placental Oxidative Stress: Insights from Animal Models to Clinical Evidences

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 414
Author(s):  
Serena Silvestro ◽  
Valeria Calcaterra ◽  
Gloria Pelizzo ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Oxidative Stress ◽  
Reproductive Function ◽  
Prenatal Hypoxia ◽  
Oxygen Species ◽  
Protective Effects ◽  
Fetal Hypoxia ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Antioxidant Agents ◽  
And Oxidative Stress

Hypoxia is a common form of intrauterine stress characterized by exposure to low oxygen concentrations. Gestational hypoxia is associated with the generation of reactive oxygen species. Increase in oxidative stress is responsible for damage to proteins, lipids and DNA with consequent impairment of normal cellular functions. The purpose of this review is to propose a summary of preclinical and clinical evidences designed to outline the correlation between fetal hypoxia and oxidative stress. The results of the studies described show that increases of oxidative stress in the placenta is responsible for changes in fetal development. Specifically, oxidative stress plays a key role in vascular, cardiac and neurological disease and reproductive function dysfunctions. Moreover, the different finding suggests that the prenatal hypoxia-induced oxidative stress is associated with pregnancy complications, responsible for changes in fetal programming. In this way, fetal hypoxia predisposes the offspring to congenital anomalies and chronic diseases in future life. Several antioxidant agents, such as melatonin, erythropoietin, vitamin C, resveratrol and hydrogen, shown potential protective effects in prenatal hypoxia. However, future investigations will be needed to allow the implementation of these antioxidants in clinical practice for the promotion of health in early intrauterine life, in fetuses and children.

scholarly journals Arginine Biosynthesis Modulates Pyoverdine Production and Release in Pseudomonas putida as Part of the Mechanism of Adaptation to Oxidative Stress

2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Laura Barrientos-Moreno ◽  
María Antonia Molina-Henares ◽  
Marta Pastor-García ◽  
María Isabel Ramos-González ◽  
Manuel Espinosa-Urgel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Amino Acid ◽  
Pseudomonas Putida ◽  
Reactive Oxygen ◽  
Full Detail ◽  
Oxygen Species ◽  
Arginine Biosynthesis ◽  
Content Type ◽  
And Oxidative Stress

ABSTRACT Iron is essential for most life forms. Under iron-limiting conditions, many bacteria produce and release siderophores—molecules with high affinity for iron—which are then transported into the cell in their iron-bound form, allowing incorporation of the metal into a wide range of cellular processes. However, free iron can also be a source of reactive oxygen species that cause DNA, protein, and lipid damage. Not surprisingly, iron capture is finely regulated and linked to oxidative-stress responses. Here, we provide evidence indicating that in the plant-beneficial bacterium Pseudomonas putida KT2440, the amino acid l-arginine is a metabolic connector between iron capture and oxidative stress. Mutants defective in arginine biosynthesis show reduced production and release of the siderophore pyoverdine and altered expression of certain pyoverdine-related genes, resulting in higher sensitivity to iron limitation. Although the amino acid is not part of the siderophore side chain, addition of exogenous l-arginine restores pyoverdine release in the mutants, and increased pyoverdine production is observed in the presence of polyamines (agmatine and spermidine), of which arginine is a precursor. Spermidine also has a protective role against hydrogen peroxide in P. putida, whereas defects in arginine and pyoverdine synthesis result in increased production of reactive oxygen species. IMPORTANCE The results of this study show a previously unidentified connection between arginine metabolism, siderophore turnover, and oxidative stress in Pseudomonas putida. Although the precise molecular mechanisms involved have yet to be characterized in full detail, our data are consistent with a model in which arginine biosynthesis and the derived pathway leading to polyamine production function as a homeostasis mechanism that helps maintain the balance between iron uptake and oxidative-stress response systems.

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