scholarly journals Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

2019 ◽  
Vol 20 (13) ◽  
pp. 3208 ◽  
Author(s):  
Fabiane Valentini Francisqueti-Ferron ◽  
Artur Junio Togneri Ferron ◽  
Jéssica Leite Garcia ◽  
Carol Cristina Vágula de Almeida Silva ◽  
Mariane Róvero Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Factor ◽  
Future Research ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Age Related ◽  
Basic Concepts

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

scholarly journals Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Juliana F. Saldanha ◽  
Viviane de O. Leal ◽  
Peter Stenvinkel ◽  
José Carlos Carraro-Eduardo ◽  
Denise Mafra
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Related Factor ◽  
Nuclear Factor ◽  
Family Protein ◽  
Nrf2 Activation ◽  
And Oxidative Stress

Resveratrol, a phenolic compound found in various plants, including grapes, berries, and peanuts, shows promise for the treatment of cancer, aging, type 2 diabetes, and cardiovascular diseases. Resveratrol can promotetranscription factor nuclear factor-erythroid 2-related factor 2(Nrf2) activation, increase the expression level of SIRT-1, which is a sirtuin family protein, and reduce mTOR pathway signaling. This compound has anti-inflammatory properties in that it inhibits or antagonizes the nuclear factor-κB (NF-κB) activity, which is a redox-sensitive transcription factor that coordinates the inflammatory response. Inflammation and oxidative stress, which are common features in patients with chronic kidney disease (CKD), are interrelated and associated with cardiovascular disease and the progression of CKD itself. Because of the modulation of the mechanisms involved in the inflammatory-oxidative stress cycle, resveratrol could play an important role in controlling CKD-related metabolic derangements. Although resveratrol supplementation in theory is a promising therapy in this patient group, there are no studies evaluating its effects. Thus, the present review aims to describe the role of resveratrol in inflammation and oxidative stress modulation and its possible benefits to patients with CKD.

scholarly journals Crosstalk between Long-Term Sublethal Oxidative Stress and Detrimental Inflammation as Potential Drivers for Age-Related Retinal Degeneration

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Lara Macchioni ◽  
Davide Chiasserini ◽  
Letizia Mezzasoma ◽  
Magdalena Davidescu ◽  
Pier Luigi Orvietani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Rpe Cells ◽  
Age Related ◽  
Oxidative Insult

Age-related retinal degenerations, including age-related macular degeneration (AMD), are caused by the loss of retinal pigmented epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD, deeply linked to the aging process, also involves oxidative stress and inflammatory responses. However, the molecular mechanisms contributing to the shift from healthy aging to AMD are still poorly understood. Since RPE cells in the retina are chronically exposed to a pro-oxidant microenvironment throughout life, we simulated in vivo conditions by growing ARPE-19 cells in the presence of 10 μM H2O2 for several passages. This long-term oxidative insult induced senescence in ARPE-19 cells without affecting cell proliferation. Global proteomic analysis revealed a dysregulated expression in proteins involved in antioxidant response, mitochondrial homeostasis, and extracellular matrix organization. The analyses of mitochondrial functionality showed increased mitochondrial biogenesis and ATP generation and improved response to oxidative stress. The latter, however, was linked to nuclear factor-κB (NF-κB) rather than nuclear factor erythroid 2–related factor 2 (Nrf2) activation. NF-κB hyperactivation also resulted in increased pro-inflammatory cytokines expression and inflammasome activation. Moreover, in response to additional pro-inflammatory insults, senescent ARPE-19 cells underwent an exaggerated inflammatory reaction. Our results indicate senescence as an important link between chronic oxidative insult and detrimental chronic inflammation, with possible future repercussions for therapeutic interventions.

scholarly journals The Redox System inC. elegans, a Phylogenetic Approach

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Andrew D. Johnston ◽  
Paul R. Ebert
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Cellular Damage ◽  
Future Research ◽  
Homologous Proteins ◽  
Redox Biology ◽  
Redox Signalling ◽  
C Elegans ◽  
Age Related

Oxidative stress is a toxic state caused by an imbalance between the production and elimination of reactive oxygen species (ROS). ROS cause oxidative damage to cellular components such as proteins, lipids, and nucleic acids. While the role of ROS in cellular damage is frequently all that is noted, ROS are also important in redox signalling. The “Redox Hypothesis" has been proposed to emphasize a dual role of ROS. This hypothesis suggests that the primary effect of changes to the redox state is modified cellular signalling rather than simply oxidative damage. In extreme cases, alteration of redox signalling can contribute to the toxicity of ROS, as well as to ageing and age-related diseases. The nematode speciesCaenorhabditis elegansprovides an excellent model for the study of oxidative stress and redox signalling in animals. We use protein sequences from central redox systems inHomo sapiens,Drosophila melanogaster, andSaccharomyces cerevisiaeto query Genbank for homologous proteins inC. elegans. We then use maximum likelihood phylogenetic analysis to compare protein families betweenC. elegansand the other organisms to facilitate future research into the genetics of redox biology.

scholarly journals MEF2D haploinsufficiency downregulates the NRF2 pathway and renders photoreceptors susceptible to light-induced oxidative stress

2017 ◽  
Vol 114 (20) ◽  
pp. E4048-E4056 ◽  
Author(s):  
Saumya Nagar ◽  
Sarah M. Noveral ◽  
Dorit Trudler ◽  
Kevin M. Lopez ◽  
Scott R. McKercher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Age Related Macular Degeneration ◽  
Mouse Retina ◽  
Nrf2 Pathway ◽  
Multifactorial Diseases ◽  
Downstream Target ◽  
Age Related ◽  
The Face ◽  
Genetic And Environmental Factors

Gaining mechanistic insight into interaction between causative factors of complex multifactorial diseases involving photoreceptor damage might aid in devising effective therapies. Oxidative stress is one of the potential unifying mechanisms for interplay between genetic and environmental factors that contribute to photoreceptor pathology. Interestingly, the transcription factor myocyte enhancer factor 2d (MEF2D) is known to be important in photoreceptor survival, as knockout of this transcription factor results in loss of photoreceptors in mice. Here, using a mild light-induced retinal degeneration model, we show that the diminished MEF2D transcriptional activity in Mef2d+/− retina is further reduced under photostimulation-induced oxidative stress. Reactive oxygen species cause an aberrant redox modification on MEF2D, consequently inhibiting transcription of its downstream target, nuclear factor (erythroid-derived 2)-like 2 (NRF2). NRF2 is a master regulator of phase II antiinflammatory and antioxidant gene expression. In the Mef2d heterozygous mouse retina, NRF2 is not up-regulated to a normal degree in the face of light-induced oxidative stress, contributing to accelerated photoreceptor cell death. Furthermore, to combat this injury, we found that activation of the endogenous NRF2 pathway using proelectrophilic drugs rescues photoreceptors from photo-induced oxidative stress and may therefore represent a viable treatment for oxidative stress-induced photoreceptor degeneration, which is thought to contribute to some forms of retinitis pigmentosa and age-related macular degeneration.

scholarly journals The Role of Nrf2 in Hearing Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Dafei Li ◽  
Haiyan Zhao ◽  
Zhong-Kai Cui ◽  
Guangyong Tian
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Cell Damage ◽  
Hearing Protection ◽  
Related Factor ◽  
Nuclear Factor ◽  
The World ◽  
Hair Cell Damage ◽  
Heavy Burden

Hearing loss is a major unresolved problem in the world, which has brought a heavy burden to society, economy, and families. Hair cell damage and loss mediated by oxidative stress are considered to be important causes of hearing loss. The nuclear factor erythroid 2–related factor 2 (Nrf2) is a major regulator of antioxidant capacity and is involved in the occurrence and development of a series of toxic and chronic diseases associated with oxidative stress. In recent years, studies on the correlation between hearing loss and Nrf2 target have continuously broadened our knowledge, and Nrf2 has become a new strategic target for the development and reuse of hearing protection drugs. This review summarized the correlation of Nrf2 in various types of hearing loss, and the role of drugs in hearing protection through Nrf2 from the literature.

scholarly journals Potential Role of Nuclear FactorκB in Diabetic Cardiomyopathy

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
O. Lorenzo ◽  
B. Picatoste ◽  
S. Ares-Carrasco ◽  
E. Ramírez ◽  
J. Egido ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Diabetic Cardiomyopathy ◽  
Nuclear Factor Kappa B ◽  
Potential Role ◽  
Heart Diseases ◽  
Cardiac Injury ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

Diabetic cardiomyopathy entails the cardiac injury induced by diabetes independently of any vascular disease or hypertension. Some transcription factors have been proposed to control the gene program involved in the setting and development of related processes. Nuclear factor-kappa B is a pleiotropic transcription factor associated to the regulation of many heart diseases. However, the nuclear factor-kappa B role in diabetic cardiomyopathy is under investigation. In this paper, we review the nuclear factor-kappa B pathway and its role in several processes that have been linked to diabetic cardiomyopathy, such as oxidative stress, inflammation, endothelial dysfunction, fibrosis, hypertrophy and apoptosis.

scholarly journals The Role of Nuclear Factor-E2-Related Factor 1 in the Oxidative Stress Response in MC3T3-E1 Osteoblastic Cells

2016 ◽  
Vol 31 (2) ◽  
pp. 336 ◽  
Author(s):  
So Young Park ◽  
Sung Hoon Kim ◽  
Hyun Koo Yoon ◽  
Chang Hoon Yim ◽  
Sung-Kil Lim
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Osteoblastic Cells ◽  
Related Factor ◽  
Nuclear Factor

scholarly journals Role of Nuclear Factor Erythroid 2–Related Factor 2 in the Oxidative Stress–Dependent Hypertension Associated With the Depletion of DJ-1

Hypertension ◽  
2015 ◽  
Vol 65 (6) ◽  
pp. 1251-1257 ◽  
Author(s):  
Santiago Cuevas ◽  
Yu Yang ◽  
Prasad Konkalmatt ◽  
Laureano D. Asico ◽  
Jun Feranil ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Related Factor ◽  
Nuclear Factor ◽  
Stress Dependent
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