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 Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

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 Nrf2 mediated ER-phagy protects against oxidative damage in intervertebral disc degeneration

2021 ◽  
Author(s):  
zhen lin ◽  
libin ni ◽  
cheng teng ◽  
zhao zhang ◽  
xinlei lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Oxidative Damage ◽  
Er Stress ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Cellular Damage ◽  
Nucleus Pulposus Cells

Intervertebral disc degeneration (IDD) increases the risk of low back pain (LBP). Oxidative stress may induce cellular damage and contribute to various diseases including IDD. Endoplasmic reticulum autophagy (ER-phagy) is a specific type of autophagy, its role in oxidative stress induced damage as well as in IDD is unknown. This study explores the role of ER-phagy in oxidative damage in intervertebral disc nucleus pulposus cells (NPCs), as well as the Nrf2/FAM134B axis in ER-phagy regulation and IDD therapy. We found ER-phagy was decreased in NPCs during oxidative stress; while FAM134B may promote ER-phagy and alleviate oxidative stress induced ER-stress and apoptosis. In addition, the nuclear transcription factor Nrf2 may promote the expression of FAM134B as well as ER-phagy, and suppress ER-stress and apoptosis in NPCs. Furthermore, overexpression of FAM134B and Nrf2 could effectively attenuate the progression of IDD in rats in vivo. These results suggest Nrf2/FAM134B mediated ER-phagy may combat oxidative damage in cells; meanwhile, ER-phagy as well as Nrf2 could be potential therapeutic targets for IDD.

scholarly journals DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy

2021 ◽  
Vol 22 (11) ◽  
pp. 5675
Author(s):  
Jinglong Chen ◽  
Danping Wang ◽  
Yibo Zong ◽  
Xiaojing Yang
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunction ◽  
Liver Diseases ◽  
Antioxidant Effect ◽  
Cellular Damage ◽  
Autophagic Flux

Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H2O2-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H2O2 and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl4 and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.

scholarly journals Reproductive Benefit of Oxidative Damage: An Oxidative Stress “Malevolence”?

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
B. Poljsak ◽  
I. Milisav ◽  
T. Lampe ◽  
I. Ostan
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Molecular Level ◽  
Antioxidant Defenses ◽  
Oxygen Species ◽  
Costs And Benefits ◽  
Evolutionary Scenario ◽  
Age Related ◽  
Oxidative Processes

High levels of reactive oxygen species (ROS) compared to antioxidant defenses are considered to play a major role in diverse chronic age-related diseases and aging. Here we present an attempt to synthesize information about proximate oxidative processes in aging (relevant to free radical or oxidative damage hypotheses of aging) with an evolutionary scenario (credited here to Dawkins hypotheses) involving tradeoffs between the costs and benefits of oxidative stress to reproducing organisms. Oxidative stress may be considered a biological imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to environment was applied to the role of oxidative stress in processes like famine and infectious diseases and their consequences at the molecular level such as mutations and cell signaling. Arguments are presented that oxidative damage is not necessarily an evolutionary mistake but may be beneficial for reproduction; this may prevail over its harmfulness to health and longevity in evolution. Thus, Dawkins' principle of biological “malevolence” may be an additional biological paradigm for explaining the consequences of oxidative stress.

scholarly journals Strategies and cognitive reserve to preserve lexical production in aging

GeroScience ◽  
2021 ◽  
Author(s):  
Monica Baciu ◽  
Sonja Banjac ◽  
Elise Roger ◽  
Célise Haldin ◽  
Marcela Perrone-Bertolotti ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Individual Variability ◽  
Future Research ◽  
Aging Effects ◽  
Main Hypothesis ◽  
Compensatory Strategies ◽  
Age Related ◽  
Complementary Domain

AbstractIn the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that “aging-modulating factors” (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF.

scholarly journals Targeting Autophagy to Counteract Obesity-Associated Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Federico Pietrocola ◽  
José Manuel Bravo-San Pedro
Keyword(s):  
Oxidative Stress ◽  
Oxygen Species ◽  
Alcoholic Fatty Liver ◽  
Redox Biology ◽  
Obesity Therapy ◽  
Treatment Of Obesity ◽  
Novel Therapeutic Strategies ◽  
Alcoholic Fatty Liver Disease ◽  
Shed Light

Reactive oxygen species (ROS) operate as key regulators of cellular homeostasis within a physiological range of concentrations, yet they turn into cytotoxic entities when their levels exceed a threshold limit. Accordingly, ROS are an important etiological cue for obesity, which in turn represents a major risk factor for multiple diseases, including diabetes, cardiovascular disorders, non-alcoholic fatty liver disease, and cancer. Therefore, the implementation of novel therapeutic strategies to improve the obese phenotype by targeting oxidative stress is of great interest for the scientific community. To this end, it is of high importance to shed light on the mechanisms through which cells curtail ROS production or limit their toxic effects, in order to harness them in anti-obesity therapy. In this review, we specifically discuss the role of autophagy in redox biology, focusing on its implication in the pathogenesis of obesity. Because autophagy is specifically triggered in response to redox imbalance as a quintessential cytoprotective mechanism, maneuvers based on the activation of autophagy hold promises of efficacy for the prevention and treatment of obesity and obesity-related morbidities.

scholarly journals FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rawshan Choudhury ◽  
Nadhim Bayatti ◽  
Richard Scharff ◽  
Ewa Szula ◽  
Viranga Tilakaratna ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Retinal Pigment ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Rpe Cells ◽  
Age Related

AbstractRetinal pigment epithelial (RPE) cells that underlie the neurosensory retina are essential for the maintenance of photoreceptor cells and hence vision. Interactions between the RPE and their basement membrane, i.e. the inner layer of Bruch’s membrane, are essential for RPE cell health and function, but the signals induced by Bruch’s membrane engagement, and their contributions to RPE cell fate determination remain poorly defined. Here, we studied the functional role of the soluble complement regulator and component of Bruch’s membrane, Factor H-like protein 1 (FHL-1). Human primary RPE cells adhered to FHL-1 in a manner that was eliminated by either mutagenesis of the integrin-binding RGD motif in FHL-1 or by using competing antibodies directed against the α5 and β1 integrin subunits. These short-term experiments reveal an immediate protein-integrin interaction that were obtained from primary RPE cells and replicated using the hTERT-RPE1 cell line. Separate, longer term experiments utilising RNAseq analysis of hTERT-RPE1 cells bound to FHL-1, showed an increased expression of the heat-shock protein genes HSPA6, CRYAB, HSPA1A and HSPA1B when compared to cells bound to fibronectin (FN) or laminin (LA). Pathway analysis implicated changes in EIF2 signalling, the unfolded protein response, and mineralocorticoid receptor signalling as putative pathways. Subsequent cell survival assays using H2O2 to induce oxidative stress-induced cell death suggest hTERT-RPE1 cells had significantly greater protection when bound to FHL-1 or LA compared to plastic or FN. These data show a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identifies a novel interaction that has implications for ocular diseases such as age-related macular degeneration.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals The Protective Role of Sestrin2 in Atherosclerotic and Cardiac Diseases

2021 ◽  
Vol 22 (3) ◽  
pp. 1200
Author(s):  
Yoshimi Kishimoto ◽  
Kazuo Kondo ◽  
Yukihiko Momiyama
Keyword(s):  
Oxidative Stress ◽  
Protective Role ◽  
Chronic Inflammatory Disease ◽  
Atherosclerotic Disease ◽  
Cardiac Diseases ◽  
Compensatory Response ◽  
Age Related ◽  
Anti Oxidant ◽  
Progression Of Atherosclerosis

Atherosclerotic disease, such as coronary artery disease (CAD), is known to be a chronic inflammatory disease, as well as an age-related disease. Excessive oxidative stress produced by reactive oxygen species (ROS) contributes to the pathogenesis of atherosclerosis. Sestrin2 is an anti-oxidant protein that is induced by various stresses such as hypoxia, DNA damage, and oxidative stress. Sestrin2 is also suggested to be associated with aging. Sestrin2 is expressed and secreted mainly by macrophages, endothelial cells, and cardiomyocytes. Sestrin2 plays an important role in suppressing the production and accumulation of ROS, thus protecting cells from oxidative damage. Since sestrin2 is reported to have anti-oxidant and anti-inflammatory properties, it may play a protective role against the progression of atherosclerosis and may be a potential therapeutic target for the amelioration of atherosclerosis. Regarding the association between blood sestrin2 levels and atherosclerotic disease, the blood sestrin2 levels in patients with CAD or carotid atherosclerosis were reported to be high. High blood sestrin2 levels in patients with such atherosclerotic disease may reflect a compensatory response to increased oxidative stress and may help protect against the progression of atherosclerosis. This review describes the protective role of sestrin2 against the progression of atherosclerotic and cardiac diseases.

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