scholarly journals The Influence of Reactive Oxygen Species in the Immune System and Pathogenesis of Multiple Sclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Mohammad javad Tavassolifar ◽  
Mohammad Vodjgani ◽  
Zahra Salehi ◽  
Maryam Izad
Keyword(s):  
Multiple Sclerosis ◽  
Reactive Oxygen Species ◽  
Immune System ◽  
T Cell ◽  
Reactive Oxygen ◽  
Autoimmune Response ◽  
Antioxidant Systems ◽  
Enzymatic Antioxidants ◽  
Oxygen Species ◽  
Nonenzymatic Antioxidants

Multiple roles have been indicated for reactive oxygen species (ROS) in the immune system in recent years. ROS have been extensively studied due to their ability to damage DNA and other subcellular structures. Noticeably, they have been identified as a pivotal second messenger for T-cell receptor signaling and T-cell activation and participate in antigen cross-presentation and chemotaxis. As an agent with direct toxic effects on cells, ROS lead to the initiation of the autoimmune response. Moreover, ROS levels are regulated by antioxidant systems, which include enzymatic and nonenzymatic antioxidants. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Nonenzymatic antioxidants contain vitamins C, A, and E, glutathione, and thioredoxin. Particularly, cellular antioxidant systems have important functions in maintaining the redox system homeostasis. This review will discuss the significant roles of ROS generation and antioxidant systems under normal conditions, in the immune system, and pathogenesis of multiple sclerosis.

scholarly journals Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species

2017 ◽  
Vol 44 (2) ◽  
pp. 532-553 ◽  
Author(s):  
Long He ◽  
Ting He ◽  
Shabnam Farrar ◽  
Linbao Ji ◽  
Tianyi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Signaling Molecules ◽  
Antioxidant Systems ◽  
Enzymatic Antioxidants ◽  
Oxygen Species ◽  
Cytochrome P450 Enzymes ◽  
Cell Death Pathway

Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, cells will produce numerous ROS, and the living organisms eventually evolve series of response mechanisms to adapt to the ROS exposure as well as utilize it as the signaling molecules. ROS molecules would trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy. Growing evidences have suggested that ROS play a critical role as the signaling molecules throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelles structure and bio-molecules, which lead to inflammatory response that is a known underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress, can transform toxic metabolites into ROS, such as superoxide anion, hydrogen peroxide and hydroxyl radical which might cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as the non-enzymatic antioxidants which collectively reduce oxidative state. Herein, we review the recent novel findings of cellular processes induced by ROS, and summarize the roles of cellular endogenous antioxidant systems as well as natural anti-oxidative compounds in several human diseases caused by ROS in order to illustrate the vital role of antioxidants in prevention against oxidative stress.

Rescue of anaemia and autoimmune responses in SOD1-deficient mice by transgenic expression of human SOD1 in erythrocytes

2009 ◽  
Vol 422 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Yoshihito Iuchi ◽  
Futoshi Okada ◽  
Rina Takamiya ◽  
Noriko Kibe ◽  
Satoshi Tsunoda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Energy Charge ◽  
Reactive Oxygen ◽  
Oxidative Modification ◽  
Autoimmune Response ◽  
Oxygen Species ◽  
Autoantibody Production ◽  
Deficient Mice ◽  
Human Sod1

Oxidative stress has been implicated as a cause of various diseases such as anaemia. We found that the SOD1 [Cu,Zn-SOD (superoxide dismutase)] gene deficiency causes anaemia, the production of autoantibodies against RBCs (red blood cells) and renal damage. In the present study, to further understand the role of oxidative stress in the autoimmune response triggered by SOD1 deficiency, we generated mice that had the hSOD1 (human SOD1) transgene under regulation of the GATA-1 promoter, and bred the transgene onto the SOD1−/− background (SOD1−/−;hSOD1tg/+). The lifespan of RBCs, levels of intracellular reactive oxygen species, and RBC content in SOD1−/−;hSOD1tg/+ mice, were approximately equivalent to those of SOD1+/+ mice. The production of antibodies against lipid peroxidation products, 4-hydroxy-2-nonenal and acrolein, as well as autoantibodies against RBCs and carbonic anhydrase II were elevated in the SOD1−/− mice, but were suppressed in the SOD1−/−;hSOD1tg/+ mice. Renal function, as judged by blood urea nitrogen, was improved in the transgenic mice. These results rule out the involvement of a defective immune system in the autoimmune response of SOD1-deficient mice, because SOD1−/−;hSOD1tg/+ mice carry the hSOD1 protein only in RBCs. Metabolomic analysis indicated a shift in glucose metabolism to the pentose phosphate pathway and a decrease in the energy charge potential of RBCs in SOD1-deficient mice. We conclude that the increase in reactive oxygen species due to SOD1 deficiency accelerates RBC destruction by affecting carbon metabolism and increasing oxidative modification of lipids and proteins. The resulting oxidation products are antigenic and, consequently, trigger autoantibody production, leading to autoimmune responses.

scholarly journals Influence of PM2.5 on spermatogenesis dysfunction via the reactive-oxygen-species-mediated Mitogen-activated-protein-kinase signaling pathway

2019 ◽  
Vol 6 (4) ◽  
pp. 77-79
Author(s):  
Ruangrong Cheepsattayakorn
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Human Sperm ◽  
Mapk Signaling ◽  
Autoimmune Response ◽  
Sperm Chromatin ◽  
Seminiferous Tubules ◽  
Oxygen Species ◽  
Mitogen Activated Protein

Approximately 15 % of the world‘s couples confront childless, and about 50 % of them are due to male reproductive disorders. Several previous studies demonstrated that PM2.5 particles has been consistently associated with critical human sperm reduction and impairment of human sperm chromatin and DNA from traffic exhaust pollution. Blood-testis barrier (BTB), a critically physical barrier between the seminiferous tubules and the blood vessels prevents sperm antigens from entering the blood circulation and facilitating and initiating an autoimmune response that contributing to spermatogenesis interference. Reactive oxygen species (ROS) are involved in the redox-sensitive signal transduction factors activation, such as Jun NH2-terminal kinase (JNK), p 38, extracellular signal-regulated kinase (ERK), and mitogen-activated protein kinases (MAPK) that critically influence BTB disruption. After PM2.5 exposure, there are decreased superoxide dismutase (SOD) expression, increased malondialdehyde (MDA) expression, increased nuclear factor erythroid 2-related factor 2 (Nrf-2) expression, increased expression of the four junctional proteins (β-catenin, Cx43, occludin, zonula occludens-1 (ZO-1)), thus improve sperm quality and quantity. PM2.5 particles markedly induce increasing phosphorylation of MAPKs via the ROS-mediated MAPK signaling pathway that causes BTB disruption, but this effect is lesser in the vitamins C and E intervention as well as increasing cleaved caspase-3 expression and the Bcl-2/Bax ratio. In conclusion, combined therapeutic administration of vitamins C and E can maintain the BTB integrity, reduce oxidative stress and cell apoptosis, and prevent toxic effects.

Progress in understanding the molecular oxygen paradox – function of mitochondrial reactive oxygen species in cell signaling

2017 ◽  
Vol 398 (11) ◽  
pp. 1209-1227 ◽  
Author(s):  
Nidhi Kuksal ◽  
Julia Chalker ◽  
Ryan J. Mailloux
Keyword(s):  
Reactive Oxygen Species ◽  
Molecular Oxygen ◽  
Reactive Oxygen ◽  
Oxygen Metabolism ◽  
Antioxidant Systems ◽  
Oxygen Species ◽  
Oxygen Paradox ◽  
Secondary Messenger ◽  
Cell Structures ◽  
By Products

AbstractThe molecular oxygen (O2) paradox was coined to describe its essential nature and toxicity. The latter characteristic of O2is associated with the formation of reactive oxygen species (ROS), which can damage structures vital for cellular function. Mammals are equipped with antioxidant systems to fend off the potentially damaging effects of ROS. However, under certain circumstances antioxidant systems can become overwhelmed leading to oxidative stress and damage. Over the past few decades, it has become evident that ROS, specifically H2O2, are integral signaling molecules complicating the previous logos that oxyradicals were unfortunate by-products of oxygen metabolism that indiscriminately damage cell structures. To avoid its potential toxicity whilst taking advantage of its signaling properties, it is vital for mitochondria to control ROS production and degradation. H2O2elimination pathways are well characterized in mitochondria. However, less is known about how H2O2production is controlled. The present review examines the importance of mitochondrial H2O2in controlling various cellular programs and emerging evidence for how production is regulated. Recently published studies showing how mitochondrial H2O2can be used as a secondary messenger will be discussed in detail. This will be followed with a description of how mitochondria use S-glutathionylation to control H2O2production.

scholarly journals The Keap1/Nrf2 Signaling Pathway in the Thyroid—2020 Update

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1082 ◽  
Author(s):  
Christina Thanas ◽  
Panos G. Ziros ◽  
Dionysios V. Chartoumpekis ◽  
Cédric O. Renaud ◽  
Gerasimos P. Sykiotis
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Antioxidant Systems ◽  
Related Factor ◽  
Oxygen Species ◽  
Nrf2 Signaling Pathway ◽  
The Face ◽  
Antioxidant Defense Systems ◽  
The One ◽  
Endogenous Antioxidant

The thyroid gland has a special relationship with oxidative stress. On the one hand, like all other tissues, it must defend itself against reactive oxygen species (ROS). On the other hand, unlike most other tissues, it must also produce reactive oxygen species in order to synthesize its hormones that contribute to the homeostasis of other tissues. The thyroid must therefore also rely on antioxidant defense systems to maintain its own homeostasis in the face of continuous self-exposure to ROS. One of the main endogenous antioxidant systems is the pathway centered on the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1). Over the last few years, multiple links have emerged between the Keap1/Nrf2 pathway and thyroid physiology, as well as various thyroid pathologies, including autoimmunity, goiter, hypothyroidism, hyperthyroidism, and cancer. In the present mini-review, we summarize recent studies shedding new light into the roles of Keap1/Nrf2 signaling in the thyroid.

scholarly journals Exogenous Tebuconazole and Trifloxystrobin Regulates Reactive Oxygen Species Metabolism Toward Mitigating Salt-Induced Damages in Cucumber Seedling

Plants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 428 ◽  
Author(s):  
Sayed Mohsin ◽  
Mirza Hasanuzzaman ◽  
M. Bhuyan ◽  
Khursheda Parvin ◽  
Masayuki Fujita
Keyword(s):  
Reactive Oxygen Species ◽  
Salt Stress ◽  
Antioxidant Defense ◽  
Ion Homeostasis ◽  
Reactive Oxygen ◽  
Cucumber Plant ◽  
Enzymatic Antioxidants ◽  
Oxygen Species ◽  
Exogenous Application ◽  
Antioxidant Defense Systems

The present study investigated the role of tebuconazole (TEB) and trifloxystrobin (TRI) on cucumber plants (Cucumis sativus L. cv. Tokiwa) under salt stress (60 mM NaCl). The cucumber plants were grown semi-hydroponically in a glasshouse. Plants were exposed to two different doses of fungicides (1.375 µM TEB + 0.5 µM TRI and 2.75 µM TEB + 1.0 µM TRI) solely and in combination with NaCl (60 mM) for six days. The application of salt phenotypically deteriorated the cucumber plant growth that caused yellowing of the whole plant and significantly destructed the contents of chlorophyll and carotenoids. The oxidative damage was created under salinity by increasing the contents of malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolytic leakage (EL) resulting in the disruption of the antioxidant defense system. Furthermore, in the leaves, stems, and roots of cucumber plants increased Na+ content was observed under salt stress, whereas the K+/Na+ ratio and contents of K+, Ca2+, and Mg2+ decreased. In contrast, the exogenous application of TEB and TRI reduced the contents of MDA, H2O2, and EL by improving the activities of enzymatic and non-enzymatic antioxidants. In addition, ion homeostasis was regulated by reducing Na+ uptake and enhanced K+ accumulation and the K+/Na+ ratio after application of TEB and TRI. Therefore, this study indicates that the exogenous application of TEB and TRI enhanced salt tolerance in cucumber plants by regulating reactive oxygen species production and antioxidant defense systems.

scholarly journals Tumor-Specific Reactive Oxygen Species Accelerators Improve Chimeric Antigen Receptor T Cell Therapy in B Cell Malignancies

2019 ◽  
Vol 20 (10) ◽  
pp. 2469 ◽  
Author(s):  
Hyeon Joo Yoo ◽  
Yibin Liu ◽  
Lei Wang ◽  
Maria-Luisa Schubert ◽  
Jean-Marc Hoffmann ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Reactive Oxygen ◽  
Treatment Resistance ◽  
Lymphocytic Leukemia ◽  
Oxygen Species ◽  
T Cell Therapy

Chimeric antigen receptor T cell (CART) therapy is currently one of the most promising treatment approaches in cancer immunotherapy. However, the immunosuppressive nature of the tumor microenvironment, in particular increased reactive oxygen species (ROS) levels, provides considerable limitations. In this study, we aimed to exploit increased ROS levels in the tumor microenvironment with prodrugs of ROS accelerators, which are specifically activated in cancer cells. Upon activation, ROS accelerators induce further generation of ROS. This leads to an accumulation of ROS in tumor cells. We hypothesized that the latter cells will be more susceptible to CARTs. CD19-specific CARTs were generated with a CD19.CAR.CD28.CD137zeta third-generation retroviral vector. Cytotoxicity was determined by chromium-51 release assay. Influence of the ROS accelerators on viability and phenotype of CARTs was determined by flow cytometry. The combination of CARTs with the ROS accelerator PipFcB significantly increased their cytotoxicity in the Burkitt lymphoma cell lines Raji and Daudi, as well as primary chronic lymphocytic leukemia cells. Exposure of CARTs to PipFcB for 48 h did not influence T cell exhaustion, viability, or T cell subpopulations. In summary, the combination of CARTs with ROS accelerators may improve adoptive immunotherapy and help to overcome tumor microenvironment-mediated treatment resistance.

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