scholarly journals Cerebrovascular and Neurological Disorders: Protective Role of NRF2

2019 ◽  
Vol 20 (14) ◽  
pp. 3433 ◽  
Author(s):  
Farzane Sivandzade ◽  
Aditya Bhalerao ◽  
Luca Cucullo
Keyword(s):  
System Integration ◽  
Intracellular Signaling ◽  
Defense Mechanisms ◽  
Cerebrovascular Disorders ◽  
Protective Role ◽  
Related Factor ◽  
Therapeutic Approaches ◽  
Cellular Defense ◽  
Lateral Sclerosis

Cellular defense mechanisms, intracellular signaling, and physiological functions are regulated by electrophiles and reactive oxygen species (ROS). Recent works strongly considered imbalanced ROS and electrophile overabundance as the leading cause of cellular and tissue damage, whereas oxidative stress (OS) plays a crucial role for the onset and progression of major cerebrovascular and neurodegenerative pathologies. These include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), stroke, and aging. Nuclear factor erythroid 2-related factor (NRF2) is the major modulator of the xenobiotic-activated receptor (XAR) and is accountable for activating the antioxidative response elements (ARE)-pathway modulating the detoxification and antioxidative responses of the cells. NRF2 activity, however, is also implicated in carcinogenesis protection, stem cells regulation, anti-inflammation, anti-aging, and so forth. Herein, we briefly describe the NRF2–ARE pathway and provide a review analysis of its functioning and system integration as well as its role in major CNS disorders. We also discuss NRF2-based therapeutic approaches for the treatment of neurodegenerative and cerebrovascular disorders.

scholarly journals The Role of NRF2 in Mycobacterial Infection

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1861
Author(s):  
Masashi Matsuyama ◽  
Mizu Nonaka ◽  
Masayuki Nakajima ◽  
Yuko Morishima ◽  
Yukio Ishii ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Mycobacterial Infection ◽  
Antioxidant Response ◽  
Protective Role ◽  
Related Factor ◽  
Gene Expressions ◽  
Resistant Tuberculosis ◽  
Avium Infection ◽  
Mycobacterium Avium Infection

The incidence of pulmonary nontuberculous mycobacterial (NTM) infection is increasing worldwide, and its clinical outcomes with current chemotherapies are unsatisfactory. The incidence of tuberculosis (TB) is still high in Africa, and the existence of drug-resistant tuberculosis is also an important issue for treatment. To discover and develop new efficacious anti-mycobacterial treatments, it is important to understand the host-defense mechanisms against mycobacterial infection. Nuclear erythroid 2 p45-related factor-2 (NRF2) is known to be a major regulator of various antioxidant response element (ARE)-driven cytoprotective gene expressions, and its protective role has been demonstrated in infections. However, there are not many papers or reviews regarding the role of NRF2 in mycobacterial infectious disease. Therefore, this review focuses on the role of NRF2 in the pathogenesis of Mycobacterium tuberculosis and Mycobacterium avium infection.

scholarly journals ROS Defense Systems and Terminal Oxidases in Bacteria

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 839
Author(s):  
Vitaliy B. Borisov ◽  
Sergey A. Siletsky ◽  
Martina R. Nastasi ◽  
Elena Forte
Keyword(s):  
Defense Mechanisms ◽  
Protective Role ◽  
Superoxide Dismutases ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Terminal Oxidases ◽  
Defense Systems ◽  
Respiratory Chains ◽  
Scavenging Enzymes

Reactive oxygen species (ROS) comprise the superoxide anion (O2·−), hydrogen peroxide (H2O2), hydroxyl radical (·OH), and singlet oxygen (1O2). ROS can damage a variety of macromolecules, including DNA, RNA, proteins, and lipids, and compromise cell viability. To prevent or reduce ROS-induced oxidative stress, bacteria utilize different ROS defense mechanisms, of which ROS scavenging enzymes, such as superoxide dismutases, catalases, and peroxidases, are the best characterized. Recently, evidence has been accumulating that some of the terminal oxidases in bacterial respiratory chains may also play a protective role against ROS. The present review covers this role of terminal oxidases in light of recent findings.

The role of corneal crystallins in the cellular defense mechanisms against oxidative stress

2008 ◽  
Vol 19 (2) ◽  
pp. 100-112 ◽  
Author(s):  
Natalie Lassen ◽  
William J. Black ◽  
Tia Estey ◽  
Vasilis Vasiliou
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Cellular Defense

scholarly journals The Protective Role of Resveratrol against Arsenic Trioxide-Induced Cardiotoxicity

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Weiqian Zhang ◽  
Changming Guo ◽  
Ruifeng Gao ◽  
Ming Ge ◽  
Yanzhu Zhu ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Cardiac Dysfunction ◽  
Oxidative Dna Damage ◽  
Antioxidant Properties ◽  
Reactive Oxygen Species Generation ◽  
Protective Role ◽  
Natural Food ◽  
Heme Oxygenase 1 ◽  
Related Factor

Arsenic trioxide (As2O3) shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Unfortunately, limiting the application of this effective agent to APL patients is severe cardiotoxicity. Resveratrol, the natural food-derived polyphenolic compound, is well known for its antioxidant properties and protects the cardiovascular system. But the potential role of resveratrol against As2O3in heart via nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) is unclear. The present study evaluated the effects of pretreatment with resveratrol and As2O3on oxidative stress and cardiac dysfunction in rat. In the present study, resveratrol decreased As2O3-induced reactive oxygen species generation, oxidative DNA damage, and pathological alterations. In addition, cardiac dysfunction parameters, intracellular calcium and arsenic accumulation, glutathione redox ratio, and cAMP deficiency levels were observed in As2O3-treated rats; these changes were attenuated by resveratrol. Furthermore, resveratrol significantly prohibited the downregulation of both Nrf2 and HO-1 gene expressions that were downregulated by As2O3, whereas resveratrol did not alter As2O3-induced nitric oxide formation. Thus, the protective role of resveratrol against As2O3-induced cardiotoxicity is implemented by the maintenance of redox homeostasis (Nrf2-HO-1 pathway) and facilitating arsenic efflux. Our findings suggest coadministration with resveratrol, and As2O3might provide a novel therapeutic strategy for APL.

scholarly journals The Protective Role of Feruloylserotonin in LPS-Induced HaCaT Cells

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3064 ◽  
Author(s):  
Yuzhu He ◽  
Byung-gook Kim ◽  
Hye-Eun Kim ◽  
Qiaochu Sun ◽  
Shuhan Shi ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Protective Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Hacat Cells ◽  
Protective Effects ◽  
Hydroxycinnamic Acid Amides ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

Epidermal inflammation is caused by various bacterial infectious diseases that impair the skin health. Feruloylserotonin (FS) belongs to the hydroxycinnamic acid amides of serotonin, which mainly exists in safflower seeds and has been proven to have anti-inflammatory and antioxidant activities. Human epidermis mainly comprises keratinocytes whose inflammation causes skin problems. This study investigated the protective effects of FS on the keratinocyte with lipopolysaccharides (LPS)-induced human HaCaT cells and elucidated its underlying mechanisms of action. The mechanism was investigated by analyzing cell viability, PGE2 levels, cell apoptosis, nuclear factor erythroid 2-related factor 2 (Nrf2) translocation, and TLR4/NF-κB pathway. The anti-inflammatory effects of FS were assessed by inhibiting the inflammation via down-regulating the TLR4/NF-κB pathway. Additionally, FS promoted Nrf2 translocation to the nucleus, indicating that FS showed anti-oxidative activities. Furthermore, the antioxidative and anti-inflammatory effects of FS were found to benefit each other, but were independent. Thus, FS can be used as a component to manage epidermal inflammation due to its anti-inflammatory and anti-oxidative properties.

scholarly journals Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Massimo Tortarolo ◽  
Daniele Lo Coco ◽  
Pietro Veglianese ◽  
Antonio Vallarola ◽  
Maria Teresa Giordana ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune System ◽  
Disease Progression ◽  
Protective Role ◽  
Progression Rate ◽  
Neuron Death ◽  
Multisystem Disease ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFαis one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFαlevels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear. Our group and others have recently reported opposite involvements of TNFR1 and TNFR2 in motor neuron death. TNFR2 mediates TNFαtoxic effects on these neurons presumably through the activation of MAP kinase-related pathways. On the other hand, TNFR2 regulates the function and proliferation of regulatory T cells (Treg) whose expression is inversely correlated with the disease progression rate in ALS patients. In addition, TNFαis considered a procachectic factor with a direct catabolic effect on skeletal muscles, causing wasting. We review and discuss the role of TNFαin ALS in the light of its multisystem nature.

scholarly journals Role of Resveratrol in Regulating Cutaneous Functions

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Si Wen ◽  
Jiechen Zhang ◽  
Bin Yang ◽  
Peter M. Elias ◽  
Mao-Qiang Man
Keyword(s):  
Protective Role ◽  
The Body ◽  
Sirtuin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Keratinocyte Differentiation ◽  
Related Factor ◽  
Keratinocyte Proliferation ◽  
Mitogen Activated Protein ◽  
Peptide Expression

Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions. Resveratrol, a natural ingredient, displays multiple benefits for various systems/organs, including the skin. The benefits of resveratrol for cutaneous functions include stimulation of keratinocyte differentiation and antimicrobial peptide expression, inhibition of keratinocyte proliferation and cutaneous inflammation, UV protection, anticancer, antiaging, and inhibition of melanogenesis. The mechanisms of action of resveratrol include activation of sirtuin 1 and nuclear factor erythroid 2-related factor 2, and inhibition of mitogen-activated protein kinase signaling. Evidence suggests that topical resveratrol could be a valuable alternative not only for daily skin care, but also for the prevention and treatment of various cutaneous disorders. This review summarizes the benefits of resveratrol for cutaneous functions.

scholarly journals The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury

2017 ◽  
Vol 312 (2) ◽  
pp. L155-L162 ◽  
Author(s):  
Hailin Zhao ◽  
Shiori Eguchi ◽  
Azeem Alam ◽  
Daqing Ma
Keyword(s):  
Lung Injury ◽  
Therapeutic Potential ◽  
Antioxidant Response ◽  
Protective Role ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Nuclear Factor ◽  
Obstructive Pulmonary Disease ◽  
Antioxidant Response Elements

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents, and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2-antioxidant pathway has been shown to be important in the protection against various lung injuries including acute lung injury/acute respiratory distress syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and allergy and was widely examined for new therapeutic targets. The present review explores the protective role of Nrf-2 against lung injury and the therapeutic potential in targeting Nrf-2.

scholarly journals The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Regina Brigelius-Flohé ◽  
Mike Müller ◽  
Doris Lippmann ◽  
Anna Patricia Kipp
Keyword(s):  
Cancer Cells ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Related Factor ◽  
Cellular Defense ◽  
Thioredoxin Reductase 1 ◽  
Cancer Initiation ◽  
Yin And Yang ◽  
Support Tumor Growth

The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising candidate for cancer prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and glutathione peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as does a TrxR1 knockout making a synergism between both systems plausible. Although this might hold true for healthy cells, the interplay may turn into the opposite in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2 will make cancer cells chemoresistant and will protect them against oxidative damage. The essential role of TrxR1 in maintaining proliferation makes its upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2 will help to inhibit cancer initiation and inflammation-triggered promotion, but its growth supporting potential will also support tumor growth. This paper considers beneficial and adverse consequences of the activation of Nrf2 and the selenoproteins which appear to depend on the cancer stage.

scholarly journals Anti-Diabetic Countermeasures Against Tobacco Smoke-Dependent Cerebrovascular Toxicity: Use and Effect of Rosiglitazone

2019 ◽  
Vol 20 (17) ◽  
pp. 4225 ◽  
Author(s):  
Farzane Sivandzade ◽  
Luca Cucullo
Keyword(s):  
Cerebrovascular Disorders ◽  
Protective Role ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cerebrovascular Dysfunction ◽  
Public Health Hazards

Tobacco smoking (TS) is one of the most addictive habit sand a main public health hazards, impacting the vascular endothelium through oxidative stress (OS) stimuli, exposure to nicotine, and smoking-induced inflammation in a dose-dependent manner. Increasing evidence also suggested that TS increases glucose intolerance and the risk factor of developing type-2 diabetes mellitus (2DM), which, along with TS, is connected to blood–brain barrier (BBB) injuries, and heightens the risk of cerebrovascular disorders. Although the exact mechanism of rosiglitazone (RSG) is unknown, our previous in vitro work showed how RSG, an oral anti-diabetic drug belonging to the family of thiazolidinedione class, can protect BBB integrity through enhancement of nuclear factor erythroid 2-related factor (Nrf2) activity. Herein, we have validated the protective role of rosiglitazone against TS-induced BBB impairment in vivo. Our results revealed that RSG as a peroxisome proliferator-activated receptor gamma (PPARγ), activates counteractive mechanisms primarily associated with the upregulation of Nrf2 and PPARγ pathways which reduce TS-dependent toxicity at the cerebrovascular level. In line with these findings, our results show that RSG reduces inflammation and protects BBB integrity. In conclusion, RSG offers a novel and promising therapeutic application to reduce TS-induced cerebrovascular dysfunction through activation of the PPARγ-dependent and/or PPARγ-independent Nrf2 pathway.

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