scholarly journals Autophagy Deficiency Leads to Impaired Antioxidant Defense via p62-FOXO1/3 Axis

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Lin Zhao ◽  
Hao Li ◽  
Yan Wang ◽  
Adi Zheng ◽  
Liu Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Antioxidant Defense ◽  
Degradation Mechanism ◽  
Redox Homeostasis ◽  
Intracellular Degradation ◽  
Cellular Models ◽  
Chemical Inhibitors ◽  
The Impact

Autophagy, an intracellular degradation mechanism eliminating unused or damaged cytoplasmic components for recycling, is often activated in response to diverse types of stress, profoundly influencing cellular physiology or pathophysiology. Upon encountering oxidative stress, autophagy acts rapidly and effectively to remove oxidized proteins or organelles, including damaged mitochondria that generate more ROS, thereby indirectly contributing to the maintenance of redox homeostasis. Emerging studies are shedding light on the crosstalks among autophagy, mitochondria, and oxidative stress; however, whether and how autophagy could directly modulate antioxidant defense and redox homeostasis remains unaddressed. Here, we showed mitochondrial dysfunction, elevated ROS level, impaired antioxidant enzymes, and loss of FOXO1/3 in autophagy deficiency cellular models established by either chemical inhibitors or knocking down/out key molecules implementing autophagy, and overexpression of FOXO1/3 restored antioxidant enzymes hence suppressed elevated ROS; knockdown of p62 increased protein level of FOXO1/3 and recovered FOXO1 in Atg5-knockdown cells. Our data demonstrates that the loss of FOXO1/3 is responsible for the impairment of antioxidant enzymes and the consequent elevation of ROS, and accumulation of p62 under condition of autophagy deficiency might be mediating the loss of FOXO1/3. Furthermore, we found in an animal model that the p62-FOXO1/3 axis could be dominant in aging liver but not in type 2 diabetic liver. Together, these evidences uncover the p62-FOXO1/3 axis as the molecular cue that underlies the impairment of antioxidant defense in autophagy deficiency and suggest its potential involvement in aging, substantiating the impact of inadequate autophagy on mitochondria and redox homeostasis.

Assessment of Superoxide Dismutase and Catalase Evolution in Different Stages of an Experimental Endometriosis

2017 ◽  
Vol 68 (6) ◽  
pp. 1381-1383
Author(s):  
Allia Sindilar ◽  
Carmen Lacramioara Zamfir ◽  
Eusebiu Viorel Sindilar ◽  
Alin Constantin Pinzariu ◽  
Eduard Crauciuc ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Reproductive Function ◽  
Female Rats ◽  
Oxygen Species ◽  
Efficient Treatment ◽  
Endometrial Cells ◽  
Gynecological Disorder ◽  
The Impact

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.

scholarly journals Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 986
Author(s):  
Nada S. Aboelella ◽  
Caitlin Brandle ◽  
Timothy Kim ◽  
Zhi-Chun Ding ◽  
Gang Zhou
Keyword(s):  
Oxidative Stress ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Tumor Rejection ◽  
Oxygen Species ◽  
Antitumor Effects ◽  
Key Drivers ◽  
Cancer Immunotherapies ◽  
The Impact

It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain redox homeostasis through a variety of mechanisms. The prevalent perception about ROS is that they are one of the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants that aim to mitigate tumor oxidative stress have been tested for cancer prevention or treatment, although the effectiveness of this strategy has yet to be established. In recent years, it has been increasingly appreciated that ROS have a complex, multifaceted role in the tumor microenvironment (TME), and that tumor redox can be targeted to amplify oxidative stress inside the tumor to cause tumor destruction. Accumulating evidence indicates that cancer immunotherapies can alter tumor redox to intensify tumor oxidative stress, resulting in ROS-dependent tumor rejection. Herein we review the recent progresses regarding the impact of ROS on cancer cells and various immune cells in the TME, and discuss the emerging ROS-modulating strategies that can be used in combination with cancer immunotherapies to achieve enhanced antitumor effects.

scholarly journals The Effect of Vitamin E on Oxidative Stress Indicated by Serum Malondialdehyde in Insulin-dependent Type 2 Diabetes Mellitus Patients with Retinopathy

2017 ◽  
Vol 11 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Irini P. Chatziralli ◽  
George Theodossiadis ◽  
Prodromos Dimitriadis ◽  
Michail Charalambidis ◽  
Antonios Agorastos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Vitamin E ◽  
Protective Role ◽  
Ophthalmological Examination ◽  
Significant Difference ◽  
Treatment Naïve ◽  
Insulin Dependent ◽  
The Impact

Background:Several studies have focused on oxidative stress on diabetes mellitus (DM). Our purpose was to investigate the impact of oxidative stress on progression of diabetic retinopathy (DR) in insulin-dependenttype 2DM patients, measuring serum malondialdehyde (MDA), as well as to examine the effect of vitamin E on DR progression in the above-mentioned patients.Methods:Participants in the study were 282 insulin-dependenttype 2DM patients with DR. All participants underwent a thorough ophthalmological examination, so as to grade DR, along with serum MDA measurement. All participants received 300mg vitamin E daily for 3 months and were examined again. Serum MDA pre- and post-intake of Vitamin E was the main outcome.Results:Serum MDA was positively associated with DR stage, while there was a statistically significant difference pre- and post-intake of vitamin E in all DR stages. In a subgroup analysis of patients with proliferative DR, there was a significant difference at baseline between patients who have received prior laser photocoagulation and the treatment naïve patients, while after intake of vitamin E, no statistically significant difference was noticed.Conclusion:Oxidative stress has been found to play significant role in the pathogenesis and progression of DR, while vitamin E seems to reduce MDA levels and subsequent oxidative stress, suggesting that it might have protective role in DR progression.

scholarly journals The Effect of Nitrogen Fertilization and Fusarium culmorum Inoculation on the Biomarkers of Oxidative Stress in Wheat Flag Leaves

Poljoprivreda ◽  
2021 ◽  
Vol 27 (2) ◽  
pp. 15-24
Author(s):  
Magdalena Matić ◽  
◽  
Rosemary Vuković ◽  
Karolina Vrandečić ◽  
Ivna Štolfa Čamagajevac ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Biotic Stress ◽  
Flag Leaf ◽  
Fusarium Culmorum ◽  
Antioxidant Response ◽  
The Impact ◽  
Biomarkers Of Oxidative Stress

During cultivation, wheat is exposed to several abiotic and/or biotic stress conditions that may adversely impact the wheat yield and quality. The impact of abiotic stress caused by nitrogen deficiency and biotic stress caused by phytopathogenic fungus Fusarium culmorum on biomarkers of oxidative stress in the flag leaf of nine winter wheat varieties (Ficko, U-1, Galloper, BC Mandica, BC Opsesija, Ingenio, Isengrain, Felix, and Bezostaya-1) was analyzed in this study. Hydrogen peroxide concentration and lipid peroxidation level were measured as indicators of oxidative stress, while the antioxidant response was determined by measuring the concentration of phenolic compounds and activities of antioxidant enzymes. Wheat variety and nitrogen treatment had a significant effect on all examined biomarkers of oxidative stress in the flag leaf, while the impact of Fusarium treatment was less pronounced. The most significant impact on the measured stress biomarkers had a low nitrogen level, which mainly increased hydrogen peroxide concentration and lipid peroxidation level and decreased activities of antioxidant enzymes in most varieties. The obtained results were discussed and compared with the previous study in which biochemical analyzes were performed on the wheat spike. There was no significant strong correlation between flag leaf and spike response in the measured parameters, which, in addition to the variety-specific response, also indicates a tissue-specific antioxidant response.

scholarly journals The Prognostic Role of Glutathione and Its Related Antioxidant Enzymes in the Recurrence of Hepatocellular Carcinoma

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4071
Author(s):  
Yung-Fang Hsiao ◽  
Shao-Bin Cheng ◽  
Chia-Yu Lai ◽  
Hsiao-Tien Liu ◽  
Shih-Chien Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Antioxidant Enzymes ◽  
Prognostic Significance ◽  
Tumor Resection ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Antioxidant Capacities ◽  
The Impact ◽  
Hcc Recurrence

The imbalance of high oxidative stress and low antioxidant capacities is thought to be a significant cause of the development and progression of hepatocellular carcinoma (HCC). However, the impact of oxidative stress, glutathione (GSH), and its related antioxidant enzymes on the recurrence of HCC has not been investigated. The purpose of this study was to compare the changes to oxidative stress and GSH-related antioxidant capacities before and after tumor resection in patients with HCC recurrence and non-recurrence. We also evaluated the prognostic significance of GSH and its related enzymes in HCC recurrence. This was a cross-sectional and follow-up study. Ninety-two HCC patients who were going to receive tumor resection were recruited. We followed patients’ recurrence and survival status until the end of the study, and then assigned patients into the recurrent or the non-recurrent group. The tumor recurrence rate was 52.2% during the median follow-up period of 3.0 years. Patients had significantly lower plasma malondialdehyde level, but significantly or slightly higher levels of GSH, glutathione disulfide, trolox equivalent antioxidant capacity, glutathione peroxidase (GPx), and glutathione reductase (GR) activities after tumor resection compared to the respective levels before tumor resection in both recurrent and non-recurrent groups. GSH level in HCC tissue was significantly higher than that in adjacent normal tissue in both recurrent and non-recurrent patients. Decreased plasma GPx (HR = 0.995, p = 0.01) and GR (HR = 0.98, p = 0.04) activities before tumor resection, and the increased change of GPx (post—pre-resection) (HR = 1.004, p = 0.03) activity were significantly associated with the recurrence of HCC. These findings suggest there might be a possible application of GPx or GR as therapeutic targets for reducing HCC recurrence.

scholarly journals Roles of Mitochondrial Sirtuins in Mitochondrial Function, Redox Homeostasis, Insulin Resistance and Type 2 Diabetes

2020 ◽  
Vol 21 (15) ◽  
pp. 5266 ◽  
Author(s):  
Chih-Hao Wang ◽  
Yau-Huei Wei
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mitochondrial Function ◽  
Oxidative Metabolism ◽  
Antioxidant Defense ◽  
Tricarboxylic Acid Cycle ◽  
Redox Homeostasis ◽  
Metabolic Adaptation ◽  
Pyrimidine Nucleotide

Mitochondria are the metabolic hubs that process a number of reactions including tricarboxylic acid cycle, β-oxidation of fatty acids and part of the urea cycle and pyrimidine nucleotide biosynthesis. Mitochondrial dysfunction impairs redox homeostasis and metabolic adaptation, leading to aging and metabolic disorders like insulin resistance and type 2 diabetes. SIRT3, SIRT4 and SIRT5 belong to the sirtuin family proteins and are located at mitochondria and also known as mitochondrial sirtuins. They catalyze NAD+-dependent deacylation (deacetylation, demalonylation and desuccinylation) and ADP-ribosylation and modulate the function of mitochondrial targets to regulate the metabolic status in mammalian cells. Emerging evidence has revealed that mitochondrial sirtuins coordinate the regulation of gene expression and activities of a wide spectrum of enzymes to orchestrate oxidative metabolism and stress responses. Mitochondrial sirtuins act in synergistic or antagonistic manners to promote respiratory function, antioxidant defense, insulin response and adipogenesis to protect individuals from aging and aging-related metabolic abnormalities. In this review, we focus on the molecular mechanisms by which mitochondrial sirtuins regulate oxidative metabolism and antioxidant defense and discuss the roles of their deficiency in the impairment of mitochondrial function and pathogenesis of insulin resistance and type 2 diabetes.

scholarly journals Patients with type 2 diabetes have reduced levels of plasma vitamin D3 and are well correlated with the oxidative stress parameters

2016 ◽  
Vol 7 (3) ◽  
pp. 35-40 ◽  
Author(s):  
Pinaki Saha ◽  
Sayantan Dasgupta ◽  
Santanu Sen ◽  
Arun Kumar ◽  
Utpal Kumar Biswas
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Vitamin D3 ◽  
Significant Positive Correlation ◽  
Antioxidant Defense ◽  
Significant Negative Correlation ◽  
Plasma Vitamin ◽  
Total Oxidative Stress ◽  
Type 2 Diabetic

Background: Diabetes has emerged as an epidemic in this country as well as worldwide. Increased oxidative stress and decreased antioxidant defense are established etiological factors of this multifactorial disease. Some of the recent studies reported deficiency of vitamin-D3 in type-2 diabetic patients. Aims and Objectives: This study was aimed to estimate the total oxidative stress (TOS), the total antioxidant defense (TAD) and the plasma 25-hydroxy vitamin D3 levels in patients of type-2 diabetes patients with an objective to elucidate if there is any significant correlation between the TOS, TAD and vitamin D3 levels.Materials and Methods: The study was conducted in forty patients recently diagnosed type-2 diabetic and the findings were compared with age/sex matched healthy controls. Total oxidative stress and TAD values was estimated by two simple colorimetric tests developed and standardized in our laboratory, plasma 25-hydroxy vitamin D3 by standardized ELISA method.Results  and Discussion: The levels of vitamin D3 in patients was found to be 50.17 ± 15.85ng/ml which was significantly decreased (P<0.001) when compared to healthy control group (75.42 ± 9.59 ng/ml). The plasma vitamin D3 levels show a significant positive correlation (r=0.564, P<0.001) with the TAD values and a significant negative correlation (r=-0.561, P<0.001) with the TOS values in the study subjects. There is significant positive correlation of 25-OH vitamin-D3 with antioxidant defense and significant negative correlation with oxidative stress observed in the current study, and the levels of vitamin D3 were significantly decreased in type-2 diabetes when compared to the healthy controls.Conclusion: The type-2 diabetes patients are usually associated with vitamin D3 deficiency which is significantly correlated with the oxidative stress conditions in this group of patients.Asian Journal of Medical Sciences Vol. 7(3) 2016 35-40

scholarly journals High Protein Diet Induces Oxidative Stress in Rat Cerebral Cortex and Hypothalamus

2019 ◽  
Vol 20 (7) ◽  
pp. 1547 ◽  
Author(s):  
Ewa Żebrowska ◽  
Mateusz Maciejczyk ◽  
Małgorzata Żendzian-Piotrowska ◽  
Anna Zalewska ◽  
Adrian Chabowski
Keyword(s):  
Oxidative Stress ◽  
Cerebral Cortex ◽  
Oxidative Damage ◽  
Antioxidant Defense ◽  
High Protein Diet ◽  
Brain Structures ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
The Impact

This is the first study to analyze the impact of high protein diet (HPD) on antioxidant defense, redox status, as well as oxidative damage on both a local and systemic level. Male Wistar rats were divided into two equal groups (n = 9): HPD (44% protein) and standard diet (CON; 24.2% protein). After eight weeks, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase-1 (SOD-1), reduced glutathione (GSH), uric acid (UA), total antioxidant (TAC)/oxidant status (TOS) as well as advanced glycation end products (AGE), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were analyzed in the serum/plasma, cerebral cortex, and hypothalamus of HPD and CON rats. HPD resulted in higher UA concentration and activity of GPx and CAT in the hypothalamus, whereas in the cerebral cortex these parameters remained unchanged. A significantly lower GSH content was demonstrated in the plasma and hypothalamus of HPD rats when compared to CON rats. Both brain structures expressed higher content of 4-HNE and MDA, whereas AGE was increased only in the hypothalamus of HPD animals. Despite the enhancement in antioxidant defense in the hypothalamus, this mechanism does not protect the hypothalamus from oxidative damage in rats. Hypothalamus is more susceptible to oxidative stress caused by HPD.

scholarly journals Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

2015 ◽  
Vol 308 (4) ◽  
pp. H291-H302 ◽  
Author(s):  
Niraj M. Bhatt ◽  
Miguel A. Aon ◽  
Carlo G. Tocchetti ◽  
Xiaoxu Shen ◽  
Swati Dey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Negative Impact ◽  
Antioxidant Activities ◽  
Contractile Function ◽  
Heart Function ◽  
Redox Balance ◽  
The Impact ◽  
Type 2 Diabetic

Hearts from type 2 diabetic (T2DM) subjects are chronically subjected to hyperglycemia and hyperlipidemia, both thought to contribute to oxidizing conditions and contractile dysfunction. How redox alterations and contractility interrelate, ultimately diminishing T2DM heart function, remains poorly understood. Herein we tested whether the fatty acid palmitate (Palm), in addition to its energetic contribution, rescues function by improving redox [glutathione (GSH), NAD(P)H, less oxidative stress] in T2DM rat heart trabeculae subjected to high glucose. Using cardiac trabeculae from Zucker Diabetic Fatty (ZDF) rats, we assessed the impact of low glucose (EG) and high glucose (HG), in absence or presence of Palm or insulin, on force development, energetics, and redox responses. We found that in EG ZDF and lean trabeculae displayed similar contractile work, yield of contractile work (Ycw), representing the ratio of force time integral over rate of O2 consumption. Conversely, HG had a negative impact on Ycw, whereas Palm, but not insulin, completely prevented contractile loss. This effect was associated with higher GSH, less oxidative stress, and augmented matrix GSH/thioredoxin (Trx) in ZDF mitochondria. Restoration of myocardial redox with GSH ethyl ester also rescued ZDF contractile function in HG, independently from Palm. These results support the idea that maintained redox balance, via increased GSH and Trx antioxidant activities to resist oxidative stress, is an essential protective response of the diabetic heart to keep contractile function.

scholarly journals Oxidative stress and genetic markers of suboptimal antioxidant defense in the aging brain: a theoretical review

2014 ◽  
Vol 25 (6) ◽  
Author(s):  
Lauren E. Salminen ◽  
Robert H. Paul
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Defense ◽  
Future Research ◽  
Aging Brain ◽  
Older Individuals ◽  
Glutathione S Transferase ◽  
Antioxidant Defense Enzymes ◽  
Repair Mechanisms ◽  
The Impact ◽  
The Brain

AbstractNormal aging involves a gradual breakdown of physiological processes that leads to a decline in cognitive functions and brain integrity, yet the onset and progression of decline are variable among older individuals. While many biological changes may contribute to this degree of variability, oxidative stress is a key mechanism of the aging process that can cause direct damage to cellular architecture within the brain. Oligodendrocytes are at a high risk for oxidative damage due to their role in myelin maintenance and production and limited repair mechanisms, suggesting that white matter may be particularly vulnerable to oxidative activity. Antioxidant defense enzymes within the brain, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), are crucial for breaking down the harmful end products of oxidative phosphorylation. Previous studies have revealed that allele variations of polymorphisms that encode these antioxidants are associated with abnormalities in SOD, CAT, GPx, and GST activity in the central nervous system. This review will focus on the role of oxidative stress in the aging brain and the impact of decreased antioxidant defense on brain integrity and cognitive function. Directions for future research investigations of antioxidant defense genes will also be discussed.

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