scholarly journals The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure

2019 ◽  
Vol 20 (16) ◽  
pp. 4009 ◽  
Author(s):  
Mirco Galiè ◽  
Viviana Covi ◽  
Gabriele Tabaracci ◽  
Manuela Malatesta
Keyword(s):  
Cellular Response ◽  
Tissue Injury ◽  
Scientific Evidence ◽  
Antioxidant Response ◽  
Ozone Exposure ◽  
Related Factor ◽  
Cellular Mechanisms ◽  
Medical Ozone ◽  
Living Organisms

Ozone (O3) is a natural, highly unstable atmospheric gas that rapidly decomposes to oxygen. Although not being a radical molecule, O3 is a very strong oxidant and therefore it is potentially toxic for living organisms. However, scientific evidence proved that the effects of O3 exposure are dose-dependent: high dosages stimulate severe oxidative stress resulting in inflammatory response and tissue injury, whereas low O3 concentrations induce a moderate oxidative eustress activating antioxidant pathways. These properties make O3 a powerful medical tool, which can be used as either a disinfectant or an adjuvant agent in the therapy of numerous diseases. In this paper, the cellular mechanisms involved in the antioxidant response to O3 exposure will be reviewed with special reference to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role in the efficacy of ozone therapy.

scholarly journals NRF2 Regulation by Noncoding RNAs in Cancers: The Present Knowledge and the Way Forward

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3621
Author(s):  
Federico Pio Fabrizio ◽  
Angelo Sparaneo ◽  
Lucia Anna Muscarella
Keyword(s):  
Noncoding Rna ◽  
Gene Network ◽  
Noncoding Rnas ◽  
Antioxidant Response ◽  
Present Knowledge ◽  
Cellular Damage ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Cellular Mechanisms

Nuclear factor erythroid 2-related factor 2 (NRF2) is the key transcription factor triggered by oxidative stress that moves in cells of the antioxidant response element (ARE)-antioxidant gene network against reactive oxygen species (ROS) cellular damage. In tumors, the NRF2 pathway represents one of the most intriguing pathways that promotes chemo- and radioresistance of neoplastic cells and its activity is regulated by genetic and epigenetic mechanisms; some of these being poorly investigated in cancer. The noncoding RNA (ncRNA) network is governed by microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) and modulates a variety of cellular mechanisms linked to cancer onset and progression, both at transcriptional and post-transcriptional levels. In recent years, the scientific findings about the effects of ncRNA landscape variations on NRF2 machines are rapidly increasing and need to be continuously updated. Here, we review the latest knowledge about the link between NRF2 and ncRNA networks in cancer, thus focusing on their potential translational significance as key tumor biomarkers.

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.

Neuroprotection of Saponins from Rhizoma panacis majoris in Cerebral Ischemia/Reperfusion is Related to Nrf2-Mediated Antioxidant Response: Role of Nrf2 and Bcl-2 Family Expressions

2014 ◽  
Vol 998-999 ◽  
pp. 269-274
Author(s):  
Wen Yi ◽  
Meng Qiong Shi ◽  
Guang Yao Liu ◽  
Wei Deng ◽  
Hui Lin Qin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Antioxidant Response ◽  
Related Factor ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Bioactive Component ◽  
Underlying Mechanisms

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component in Rhizoma Panacis Majoris, were reported to possess protective effects on brain injury, but the underlying mechanisms remain poorly understood. This study was performed to investigate the protective effects and possible mechanism of SRPM on cerebral ischemia/reperfusion (CI/R) injury. Neuroprotective effects of SPRM in CI/R mice was evaluated by infarct size, biochemical values, Nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family expressions. In the study, we found that SRPM exerted beneficially protective effects on CI/R injury, mainly scavenging oxidative stress-triggered overgeneration and accumulation of reactive oxygen species, improving the Nrf2-mediated antioxidant response: role of Nrf2 and Bcl-2 family expressions, and alleviating CI/R injury and cerebral cell death.

scholarly journals Role of the Nrf2-ARE Pathway in Liver Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Mi Shin ◽  
Ji Hye Yang ◽  
Sung Hwan Ki
Keyword(s):  
Liver Diseases ◽  
Target Genes ◽  
Antioxidant Response ◽  
Related Factor ◽  
Genes Expression ◽  
Wide Range ◽  
Range Of Functions ◽  
Central Organ ◽  
Essential Transcription Factor

The liver is a central organ that performs a wide range of functions such as detoxification and metabolic homeostasis. Since it is a metabolically active organ, liver is particularly susceptible to oxidative stress. It is well documented that liver diseases including hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are highly associated with antioxidant capacity. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. It is activated in response to electrophiles and induces its target genes by binding to the antioxidant response element (ARE). Therefore, the roles of the Nrf2-ARE pathway in liver diseases have been extensively investigated. Studies from several animal models suggest that the Nrf2-ARE pathway collectively exhibits diverse biological functions against viral hepatitis, alcoholic and nonalcoholic liver disease, fibrosis, and cancer via target gene expression. In this review, we will discuss the role of the Nrf2-ARE pathway in liver pathophysiology and the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases.

scholarly journals Metabolic Reprogramming and Host Tolerance: A Novel Concept to Understand Sepsis-Associated AKI

2021 ◽  
Vol 10 (18) ◽  
pp. 4184
Author(s):  
Juan Toro ◽  
Carlos L. Manrique-Caballero ◽  
Hernando Gómez
Keyword(s):  
Defense Mechanisms ◽  
Cellular Response ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Metabolic Reprogramming ◽  
Tolerance Mechanism ◽  
Risk Of Progression ◽  
Novel Concept ◽  
Host Tolerance

Acute kidney injury (AKI) is a frequent complication of sepsis that increases mortality and the risk of progression to chronic kidney disease. However, the mechanisms leading to sepsis-associated AKI are still poorly understood. The recognition that sepsis induces organ dysfunction in the absence of overt necrosis or apoptosis has led to the consideration that tubular epithelial cells (TEC) may deploy defense mechanisms to survive the insult. This concept dovetails well with the notion that the defense against infection does not only depend on the capacity of the immune system to limit the microbial load (known as resistance), but also on the capacity of cells and tissues to limit tissue injury (known as tolerance). In this review, we discuss the importance of TEC metabolic reprogramming as a defense strategy during sepsis, and how this cellular response is likely to operate through a tolerance mechanism. We discuss the fundamental role of specific regulatory nodes and of mitochondria in orchestrating this response, and how this opens avenues for the exploration of targeted therapeutic strategies to prevent or treat sepsis-associated AKI.

scholarly journals Polyunsaturated Fatty Acids as Prebiotics: Innovation or Confirmation?

Foods ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 146
Author(s):  
Emanuele Rinninella ◽  
Lara Costantini
Keyword(s):  
Fatty Acids ◽  
Linoleic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Consensus Statement ◽  
Scientific Evidence ◽  
New Frontier ◽  
Important Health ◽  
Omega 6 ◽  
Living Organisms

The International Scientific Association for Probiotics and Prebiotics (ISAPP), in its last consensus statement about prebiotics, defined polyunsaturated fatty acids (PUFAs) as “candidate prebiotics” due to a lack of complete scientific evidence. Previous studies have demonstrated the ability of microbiota to metabolize PUFAs, although the role of the resulting metabolites in the host is less known. Recent partial evidence shows that these metabolites can have important health effects in the host, reinforcing the concept of the prebiotic action of PUFAs, despite the data being mostly related to omega-6 linoleic acid and to lactobacilli taxon. However, considering that the symbionts in our gut benefit from the nutritional molecules that we include in our diet, and that bacteria, like all living organisms, cannot benefit from a single nutritional molecule, the concept of the “correct prebiotic diet” should be the new frontier in the field of gut microbiota research.

scholarly journals NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiao Xue ◽  
Chenxiao Yu ◽  
Yiting Tang ◽  
Wei Mo ◽  
Zhicheng Tang ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Expression Profiles ◽  
Antioxidant Response ◽  
High Dose ◽  
Related Factor ◽  
Skin Injury ◽  
Skin Cells ◽  
Dose Irradiation ◽  
Radiation Induced

Radiation-induced skin injury (RISI) commonly occur in cancer patients who received radiotherapy and is one of the first clinical symptoms after suffering from nuclear exposure. Oxidative damage is the major causes of RISI. Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a key mediator of the cellular antioxidant response. However, whether Nrf2 can alleviate RISI after high-dose irradiation remains unknown. In this study, we demonstrated that Nrf2-deficient (Nrf2-/-) mice were susceptible to high-dose irradiation and adenovirus-mediated overexpression of Nrf2 (ad-Nrf2) protected against radiation in skin cells. Overexpression of Nrf2 attenuated the severity of skin injury after high-dose electron beam irradiation. To uncover the mechanisms of Nrf2 involved in RISI, mRNA sequencing technology was performed to analyze the mRNA expression profiles of Ad-Nrf2 skin cells following radiation. The results revealed that a total of 127 genes were significantly changed, 55 genes were upregulated, and 72 genes were downregulated after Nrf2 overexpression. GSEA showed that Nrf2 was associated with positive regulation of genes involved in the reactive oxygen species pathway after radiation. Taken together, this study illustrated the role of Nrf2 in RISI and provided potentially strategies for ameliorating RISI.

scholarly journals The Role of the Keap1/Nrf2 Pathway in the Cellular Response to Methylmercury

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yoshito Kumagai ◽  
Hironori Kanda ◽  
Yasuhiro Shinkai ◽  
Takashi Toyama
Keyword(s):  
Cellular Response ◽  
Cultured Cells ◽  
Protein Adducts ◽  
Negative Regulator ◽  
Cellular Damage ◽  
Cellular Proteins ◽  
Related Factor ◽  
Mehg Exposure ◽  
Nrf2 Pathway

Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins with reactive thiols, resulting in the formation of protein adducts. While such protein modifications, referred to asS-mercuration, are thought to be associated with the enzyme dysfunction and cellular damage caused by MeHg exposure, the current consensus is that (1) there is a cellular response to MeHg through the activation of NF-E2-related factor 2 (Nrf2) coupled toS-mercuration of its negative regulator, Kelch-like ECH-associated protein 1 (Keap1), and (2) the Keap1/Nrf2 pathway protects against MeHg toxicity. In this review, we introduce our findings and discuss the observations of other workers concerning theS-mercuration of cellular proteins by MeHg and the importance of the Keap1/Nrf2 pathway in protection against MeHg toxicity in cultured cells and mice.

Inhibition of sphingomyelin synthase 2 relieves hypoxia-induced cardiomyocyte injury by reinforcing Nrf2/ARE activation via modulation of GSK-3β

2020 ◽  
pp. 096032712096995
Author(s):  
Aiping Jin ◽  
Haijuan Cheng ◽  
Lina Xia ◽  
Sha Ye ◽  
Cuiling Yang
Keyword(s):  
Myocardial Infarction ◽  
Potential Role ◽  
Glycogen Synthase ◽  
Tissue Injury ◽  
Cardiac Injury ◽  
Ros Generation ◽  
Related Factor ◽  
Loss Of Function ◽  
Sphingomyelin Synthase

Sphingomyelin synthase 2 (SMS2) is a vital contributor to tissue injury and affects various pathological processes. However, whether SMS2 participates in the modulation of cardiac injury in myocardial infarction has not been determined. This study aimed to evaluate the potential role of SMS2 in the regulation of cardiomyocyte injury induced by hypoxia, an in vitro model for studying myocardial infarction. Our data revealed that SMS2 expression was significantly upregulated in cardiomyocytes in response to hypoxia. Loss-of-function experiments revealed that knockdown of SMS2 markedly restored the viability of cardiomyocytes impaired by hypoxia, and attenuated hypoxia-evoked apoptosis and reactive oxygen species (ROS) generation. In contrast, cardiomyocytes that highly expressed SMS2 were more sensitive to hypoxia-induced injury. Moreover, SMS2 deficiency enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling through inactivation of glycogen synthase kinase-3β. Notably, suppression of Nrf2 markedly abrogated SMS2 knockdown-mediated cardioprotective effects on hypoxia-exposed cardiomyocytes. Our results illustrate that downregulation of SMS2 exerts a cardioprotective function by protecting cardiomyocytes from hypoxia-induced apoptosis and oxidative stress through enhancement of Nrf2 activation. Our study indicates a potential role of SMS2 in the modulation of cardiac injury, which may contribute to the progression of myocardial infarction.

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