scholarly journals Reactive oxygen species oxidize STING and suppress interferon production

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lili Tao ◽  
Andrew Lemoff ◽  
Guoxun Wang ◽  
Christina Zarek ◽  
Alexandria Lowe ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Regulation ◽  
Reactive Oxygen ◽  
Interferon Response ◽  
Cellular Respiration ◽  
Type I ◽  
Oxygen Species ◽  
Interferon Production ◽  
Dna Sensing ◽  
Cytoplasmic Dna

Reactive oxygen species (ROS) are by-products of cellular respiration that can promote oxidative stress and damage cellular proteins and lipids. One canonical role of ROS is to defend the cell against invading bacterial and viral pathogens. Curiously, some viruses, including herpesviruses, thrive despite the induction of ROS, suggesting that ROS are beneficial for the virus. However, the underlying mechanisms remain unclear. Here, we found that ROS impaired interferon response during murine herpesvirus infection and that the inhibition occurred downstream of cytoplasmic DNA sensing. We further demonstrated that ROS suppressed the type I interferon response by oxidizing Cysteine 147 on murine stimulator of interferon genes (STING), an ER-associated protein that mediates interferon response after cytoplasmic DNA sensing. This inhibited STING polymerization and activation of downstream signaling events. These data indicate that redox regulation of Cysteine 147 of mouse STING, which is equivalent to Cysteine 148 of human STING, controls interferon production. Together, our findings reveal that ROS orchestrates anti-viral immune responses, which can be exploited by viruses to evade cellular defenses.

scholarly journals Redox-regulation of Erk1/2-directed phosphatase by reactive oxygen species: Role in signaling TPA-induced growth arrest in ML-1 cells

2008 ◽  
Vol 216 (1) ◽  
pp. 276-285 ◽  
Author(s):  
Kassim Traore ◽  
Rajni Sharma ◽  
Rajesh K. Thimmulappa ◽  
Walter H. Watson ◽  
Shyam Biswal ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Regulation ◽  
Growth Arrest ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Cell type-specific differences in redox regulation and proliferation after low UVA doses

2018 ◽  
Author(s):  
Sylwia Ciesielska ◽  
Patryk Bil ◽  
Karolina Gajda ◽  
Aleksandra Poterala-Hejmo ◽  
Dorota Hudy ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Regulation ◽  
Cellular Proliferation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cell Type ◽  
Redox Systems ◽  
Human Colon Cancer ◽  
Cellular Redox ◽  
Hct116 Cells

AbstractUltraviolet A (UVA) radiation is harmful for living organisms but in low doses may stimulate cell proliferation. Our aim was to examine the relationships between exposure to different low UVA doses, cellular proliferation, and changes in cellular reactive oxygen species levels. In human colon cancer (HCT116) and melanoma (Me45) cells exposed to UVA doses comparable to environmental, the highest doses (30-50 kJ/m2) reduced clonogenic potential but some lower doses (1 and 10 kJ/m2) induced proliferation. This effect was cell type and dose specific. In both cell lines the levels of reactive oxygen species and nitric oxide fluctuated with dynamics which were influenced differently by UVA; in Me45 cells decreased proliferation accompanied the changes in the dynamics of H2O2 while in HCT116 cells those of superoxide. Genes coding for proteins engaged in redox systems were expressed differently in each cell line; transcripts for thioredoxin, peroxiredoxin and glutathione peroxidase showed higher expression in HCT116 cells whereas those for glutathione transferases and copper chaperone were more abundant in Me45 cells. We conclude that these two cell types utilize different pathways for regulating their redox status. Many mechanisms engaged in maintaining cellular redox balance have been described. Here we show that the different cellular responses to a stimulus such as a specific dose of UVA may be consequences of the use of different redox control pathways. Assays of superoxide and hydrogen peroxide level changes after exposure to UVA may clarify mechanisms of cellular redox regulation and help in understanding responses to stressing factors.

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 Reactive oxygen species and redox regulation in mesophyll and bundle sheath cells of C4 plants

2018 ◽  
Vol 69 (14) ◽  
pp. 3321-3331 ◽  
Author(s):  
Ismail Turkan ◽  
Baris Uzilday ◽  
Karl-Josef Dietz ◽  
Andrea Bräutigam ◽  
Rengin Ozgur
Keyword(s):  
Reactive Oxygen Species ◽  
Redox Regulation ◽  
Reactive Oxygen ◽  
Bundle Sheath ◽  
C4 Plants ◽  
Oxygen Species ◽  
Bundle Sheath Cells ◽  
Sheath Cells

Stimulatory Auto-Antibodies to the PDGF Receptor in Patients with Chronic GVHD.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 454-454
Author(s):  
Attilio Olivieri ◽  
Silvia Svegliati ◽  
Nadia Campelli ◽  
Michele Maria Luchetti ◽  
Silvia Trappolini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Type I Collagen ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Type I ◽  
Collagen Gene ◽  
Pdgf Receptor ◽  
Oxygen Species ◽  
Normal Human

Abstract Background Experimental data are consistent with the hypothesis that activation of the PDGF receptor (PDGFR) is characteristic of scleroderma (SSc) fibroblasts and may contribute to their activation. We have recently demonstrated that fibroblasts from SSc patients contain high Ha Ras and ROS (Reactive Oxygen Species) levels and constitutive activation of ERK1/2 (Svegliati et al: JBC in press). Furthermore, SSc patients have circulating auto-antibodies against the PDGFR which induce type I collagen gene expression in normal human fibroblasts through the Ha Ras-ERK1/2- ROS pathway (Svegliati et al: Submitted). These findings suggest that anti PDGFR auto-antibodies play a pivotal role in the pathogenesis of scleroderma. Clinical chronic graft-versus-host disease (cGVHD) can show manifestations that are very similar to those of SSc. Although it is conceivable that the two diseases can share a similar pathophysiological mechanism there are no data supporting this assumption. In view of these considerations we tested the hypothesis that patients with cGVHD have serum auto-antibodies that stimulate PDGFR and activate collagen gene expression in fibroblasts. Methods Serum from 7 patients with extensive cGVHD showing scleroderma-like features either in the skin or in the lung was analyzed for the presence of stimulatory autoantibodies to PDGFR. Patients receiving allogeneic transplantation, but without any signs of cGVHD were used as controls. The median F-U after transplant was 23 months (range 16–36) in patients with cGVH and 42 (range 9–51) in the control group. The assay was carried by incubating purified IgG of the patients with mouse embryo fibroblasts carrying inactive copies of PDGFR α or β chains (PDGFR −/−) or the same cells expressing PDGFR α or β, respectively. Production of reactive oxygen species was assayed in the presence or absence of specific PDGFR inhibitors. The antibodies were characterized by immunoprecipitation, immunoblotting and absorption experiments in primary human fibroblasts and endothelial cells. Result Stimulatory antibodies to the PDGFR were selectively found in all patients with cGVHD and fibrotic lesions. The antibodies specifically recognized PDGFR, induced tyrosine phosphorylation and ROS accumulation. Their activity was completely and selectively abolished by pre-incubation with cells expressing PDGFR α or β chains or by PDGF receptor tyrosine kinase inhibitor. Anti-PDGFR antibodies induced selectively Ha-Ras-ERK1/2 and ROS cascade and stimulated the expression of type I collagen gene and myofibroblast phenotype conversion in normal human primary fibroblasts. Antibodies were absent in all controls. Conclusions Stimulatory auto-antibodies against PDGFR represent a specific hallmark of patients with cGVHD. Their biological activity on fibroblasts strongly argues for a causal role in the pathogenesis of the disease.

scholarly journals Inside-Out Signaling Pathways from Nuclear Reactive Oxygen Species Control Pulmonary Innate Immunity

2016 ◽  
Vol 8 (2) ◽  
pp. 143-155 ◽  
Author(s):  
Sanjeev Choudhary ◽  
Istvan Boldogh ◽  
Allan R. Brasier
Keyword(s):  
Reactive Oxygen Species ◽  
Innate Immunity ◽  
Signaling Pathways ◽  
Nuclear Export ◽  
Reactive Oxygen ◽  
Small Gtpase ◽  
Early Gene ◽  
Type I ◽  
Oxygen Species ◽  
Ros Signaling

The airway mucosa is responsible for mounting a robust innate immune response (IIR) upon encountering pathogen-associated molecular patterns. The IIR produces protective gene networks that stimulate neighboring epithelia and components of the immune system to trigger adaptive immunity. Little is currently known about how cellular reactive oxygen species (ROS) signaling is produced and cooperates in the IIR. We discuss recent discoveries about 2 nuclear ROS signaling pathways controlling innate immunity. Nuclear ROS oxidize guanine bases to produce mutagenic 8-oxoguanine, a lesion excised by 8-oxoguanine DNA glycosylase1/AP-lyase (OGG1). OGG1 forms a complex with the excised base, inducing its nuclear export. The cytoplasmic OGG1:8-oxoG complex functions as a guanine nucleotide exchange factor, triggering small GTPase signaling and activating phosphorylation of the nuclear factor (NF)κB/RelA transcription factor to induce immediate early gene expression. In parallel, nuclear ROS are detected by ataxia telangiectasia mutated (ATM), a PI3 kinase activated by ROS, triggering its nuclear export. ATM forms a scaffold with ribosomal S6 kinases, inducing RelA phosphorylation and resulting in transcription-coupled synthesis of type I and type III interferons and CC and CXC chemokines. We propose that ATM and OGG1 are endogenous nuclear ROS sensors that transmit nuclear signals that coordinate with outside-in pattern recognition receptor signaling, regulating the IIR.

Reactive oxygen species from type-I photosensitized reactions contribute to the light-induced wilting of dark-grown pea (Pisum sativum) epicotyls

2010 ◽  
Vol 138 (4) ◽  
pp. 485-492 ◽  
Author(s):  
Éva Hideg ◽  
Beáta Vitányi ◽  
Annamária Kósa ◽  
Katalin Solymosi ◽  
Károly Bóka ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pisum Sativum ◽  
Reactive Oxygen ◽  
Type I ◽  
Oxygen Species

scholarly journals PHOTODYNAMIC THERAPY: NEW LIGHT IN MEDICINE WORLD

2010 ◽  
Vol 8 (2) ◽  
pp. 279-291 ◽  
Author(s):  
Venny Santosa ◽  
Leenawaty Limantara
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Side Effects ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Type I ◽  
Oxygen Species ◽  
Type Ii ◽  
Light Spectrum ◽  
Medical Field

Photodynamic therapy (PDT) is a considerably new kind of photochemotherapeutic treatment in medical field. It combines the use of three components, which are a photosensitizer, light and oxygen. Photosensitizer is a compound activated by light. The application can be oral, topical or intravenous. It usually member of porphyrin group with ampiphilic characteristics. Photosensitizer can be of generation I, II or III, each generation step develops more specificity, selectivity and deeper tissue application. This review will discuss photosensitizer development consecutively, with its benefit and lackness. The light used is usually on red region, while the oxygen is involved in reactive oxygen species generation. Its mechanism action can go through either in type I or type II reaction. This kind of therapy is usually being used in oncology, especially in superficial and in-lining cancers, dermatology and ophthalmology field. This therapy can be safely given to patients with complication and has distinct advantages compare with other treatment such as chemotherapy and surgery. It also considerably has lesser side effects and risks. Broader application is being developed through various experiments and photosensitizer modification.   Keywords: light spectrum, photoactivation, photodynamic therapy, photosensitizer

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