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

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.

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Control of Reactive Oxygen Species for the Prevention of Parkinson’s Disease: The Possible Application of Flavonoids

Antioxidants ◽

10.3390/antiox9070583 ◽

2020 ◽

Vol 9 (7) ◽

pp. 583 ◽

Cited By ~ 6

Author(s):

Tae Yeon Kim ◽

Eunju Leem ◽

Jae Man Lee ◽

Sang Ryong Kim

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Glycogen Synthase ◽

Reactive Oxygen ◽

Adult Brain ◽

Related Factor ◽

Oxygen Species ◽

Antioxidant Defense Systems

Oxidative stress reflects an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems, and it can be associated with the pathogenesis and progression of neurodegenerative diseases such as multiple sclerosis, stroke, and Parkinson’s disease (PD). The application of antioxidants, which can defend against oxidative stress, is able to detoxify the reactive intermediates and prevent neurodegeneration resulting from excessive ROS production. There are many reports showing that numerous flavonoids, a large group of natural phenolic compounds, can act as antioxidants and the application of flavonoids has beneficial effects in the adult brain. For instance, it is well known that the long-term consumption of the green tea-derived flavonoids catechin and epigallocatechin gallate (EGCG) can attenuate the onset of PD. Also, flavonoids such as ampelopsin and pinocembrin can inhibit mitochondrial dysfunction and neuronal death through the regulation of gene expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Additionally, it is well established that many flavonoids exhibit anti-apoptosis and anti-inflammatory effects through cellular signaling pathways, such as those involving (ERK), glycogen synthase kinase-3β (GSK-3β), and (Akt), resulting in neuroprotection. In this review article, we have described the oxidative stress involved in PD and explained the therapeutic potential of flavonoids to protect the nigrostriatal DA system, which may be useful to prevent PD.

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Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease

Cells ◽

10.3390/cells9061342 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1342 ◽

Cited By ~ 4

Author(s):

Maria V. Irazabal ◽

Vicente E. Torres

Keyword(s):

Reactive Oxygen Species ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Reactive Oxygen ◽

Public Health Problem ◽

Redox Signaling ◽

Cellular Damage ◽

Antioxidant Systems ◽

Related Factor ◽

Oxygen Species

Chronic kidney disease (CKD) remains a worldwide public health problem associated with serious complications and increased mortality rates. Accumulating evidence indicates that elevated intracellular levels of reactive oxygen species (ROS) play a major role in the pathogenesis of CKD. Increased intracellular levels of ROS can lead to oxidation of lipids, DNA, and proteins, contributing to cellular damage. On the other hand, ROS are also important secondary messengers in cellular signaling. Consequently, normal kidney cell function relies on the “right” amount of ROS. Mitochondria and NADPH oxidases represent major sources of ROS in the kidney, but renal antioxidant systems, such as superoxide dismutase, catalase, or glutathione peroxidase counterbalance ROS-mediated injury. This review discusses the main sources of ROS and antioxidant systems in the kidney, and redox signaling pathways leading to inflammation and fibrosis, which result in abnormal kidney function and CKD progression. We further discuss the important role of the nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating antioxidant responses, and other mechanisms of redox signaling.

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Resistance Training, Antioxidant Status, and Antioxidant Supplementation

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.2018-0339 ◽

2019 ◽

Vol 29 (5) ◽

pp. 539-547 ◽

Cited By ~ 5

Author(s):

Ahmed Ismaeel ◽

Michael Holmes ◽

Evlampia Papoutsi ◽

Lynn Panton ◽

Panagiotis Koutakis

Keyword(s):

Reactive Oxygen Species ◽

Skeletal Muscle ◽

Resistance Training ◽

Antioxidant Status ◽

Reactive Oxygen ◽

Oxygen Species ◽

Antioxidant Supplementation ◽

Antioxidant Defense Systems ◽

Antioxidant Supplements ◽

Endogenous Antioxidant

Resistance training is known to promote the generation of reactive oxygen species. Although this can likely upregulate the natural, endogenous antioxidant defense systems, high amounts of reactive oxygen species can cause skeletal muscle damage, fatigue, and impair recovery. To prevent these, antioxidant supplements are commonly consumed along with exercise. Recently, it has been shown that these reactive oxygen species are important for the cellular adaptation process, acting as redox signaling molecules. However, most of the research regarding antioxidant status and antioxidant supplementation with exercise has focused on endurance training. In this review, the authors discuss the evidence for resistance training modulating the antioxidant status. They also highlight the effects of combining antioxidant supplementation with resistance training on training-induced skeletal muscle adaptations.

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NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-β1/SMADs Pathway

Digestive Diseases and Sciences ◽

10.1007/s10620-017-4710-z ◽

2017 ◽

Vol 63 (2) ◽

pp. 366-380 ◽

Cited By ~ 9

Author(s):

Yadi Guan ◽

Yue Tan ◽

Weiyu Liu ◽

Jun Yang ◽

Dongxu Wang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Related Factor ◽

Oxygen Species ◽

Intestinal Fibrosis ◽

Tgf Β1

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

Biological Chemistry ◽

10.1515/hsz-2017-0160 ◽

2017 ◽

Vol 398 (11) ◽

pp. 1209-1227 ◽

Cited By ~ 35

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.

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

Plants ◽

10.3390/plants8100428 ◽

2019 ◽

Vol 8 (10) ◽

pp. 428 ◽

Cited By ~ 5

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.

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

Autoimmune Diseases ◽

10.1155/2020/5793817 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 2

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.

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Superoxide Dismutase Influences the Virulence of Cryptococcus neoformans by Affecting Growth within Macrophages

Infection and Immunity ◽

10.1128/iai.71.1.173-180.2003 ◽

2003 ◽

Vol 71 (1) ◽

pp. 173-180 ◽

Cited By ~ 179

Author(s):

Gary M. Cox ◽

Thomas S. Harrison ◽

Henry C. McDade ◽

Carlos P. Taborda ◽

Garrett Heinrich ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Superoxide Dismutase ◽

Cryptococcus Neoformans ◽

Fungal Infections ◽

Reactive Oxygen ◽

Oxygen Species ◽

Wild Type ◽

Pathogenic Yeast ◽

Antioxidant Defense Systems

ABSTRACT Superoxide dismutase (SOD) is an enzyme that converts superoxide radicals into hydrogen peroxide and molecular oxygen and has been shown to contribute to the virulence of many human-pathogenic bacteria through its ability to neutralize toxic levels of reactive oxygen species generated by the host. SOD has also been speculated to be important in the pathogenesis of fungal infections, but the role of this enzyme has not been rigorously investigated. To examine the contribution of SOD to the pathogenesis of fungal infections, we cloned the Cu,Zn SOD-encoding gene (SOD1) from the human-pathogenic yeast Cryptococcus neoformans and made mutants via targeted disruption. The sod1 mutant strains had marked decreases in SOD activity and were strikingly more susceptible to reactive oxygen species in vitro. A sod1 mutant was significantly less virulent than the wild-type strain and two independent reconstituted strains, as measured by cumulative survival in the mouse inhalational model. In vitro studies established that the sod1 strain had attenuated growth compared to the growth of the wild type and a reconstituted strain inside macrophages producing reduced amounts of nitric oxide. These findings demonstrate that (i) the Cu,Zn SOD contributes to virulence but is not required for pathogenicity in C. neoformans; (ii) the decreased virulence of the sod1 strain may be due to increased susceptibility to oxygen radicals within macrophages; and (iii) other antioxidant defense systems in C. neoformans can compensate for the loss of the Cu,Zn SOD in vivo.

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