scholarly journals Transcriptional regulators of redox balance and other homeostatic processes with the potential to alter neurodegenerative disease trajectory

2017 ◽  
Vol 45 (6) ◽  
pp. 1295-1303 ◽  
Author(s):  
Scott W. Burnside ◽  
Giles E. Hardingham
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disease ◽  
Glutamate Uptake ◽  
Redox Homeostasis ◽  
Neuronal Loss ◽  
Redox Balance ◽  
Antioxidant Defences ◽  
Disease Trajectory ◽  
Inflammatory Status ◽  
The Brain

Diverse neurodegenerative diseases share some common aspects to their pathology, with many showing evidence of disruption to the brain's numerous homeostatic processes. As such, imbalanced inflammatory status, glutamate dyshomeostasis, hypometabolism and oxidative stress are implicated in many disorders. That these pathological processes can influence each other both up- and downstream makes for a complicated picture, but means that successfully targeting one area may have an effect on others. This targeting requires an understanding of the mechanisms by which homeostasis is maintained during health, in order to uncover strategies to boost homeostasis in disease. A case in point is redox homeostasis, maintained by antioxidant defences co-ordinately regulated by the transcription factor Nrf2, and capable of preventing not only oxidative stress but also inflammation and neuronal loss in neurodegenerative disease models. The emergence of other master regulators of homeostatic processes in the brain controlling inflammation, mitochondrial biogenesis, glutamate uptake and energy metabolism raises the question as to whether they too can be targeted to alter disease trajectory.

scholarly journals Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1118
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Melita Salkovic-Petrisic
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Redox Homeostasis ◽  
Brain State ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.

Effects of iron-related compounds and bilirubin on redox homeostasis in endometriosis and its malignant transformations

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hiroshi Shigetomi ◽  
Shogo Imanaka ◽  
Hiroshi Kobayashi
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Heme Iron ◽  
Total Iron ◽  
University Hospital ◽  
Free Iron ◽  
Significant Difference ◽  
Iron Heme ◽  
Related Compounds

Abstract Objectives The balance between oxidative stress and antioxidant defense has been reported to differ between women with endometriosis and patients with its malignant transformation. The aim of this study is to investigate changes in redox balance in endometriosis and endometriosis-related ovarian cancer (EAOC) by simultaneously measuring iron-related compounds and bilirubin. Methods This study included 235 patients with a histopathologically confirmed diagnosis of endometriosis (n=178) and EAOC (n=57). Cyst fluid samples were collected in Nara Medical University hospital from January 2013 to May 2019. The levels of iron-related compounds (total iron, heme iron, free iron, oxyhemoglobin [oxyHb], methemoglobin [metHb], and metHb/oxyHb ratio) and bilirubin were measured. Results Total iron, heme iron, free iron, metHb/oxyHb ratio, and bilirubin were significantly elevated in endometriosis compared to EAOC. In both endometriosis and EAOC, iron-related compounds in the cyst were correlated with each other. There was no statistically significant difference in oxyHb and metHb levels between the two groups, but the metHb/oxyHb ratio was significantly higher in endometriosis than in EAOC. Bilirubin was positively correlated with total iron and free iron in EAOC, but there was no correlation between bilirubin and iron-related compounds in endometriosis. Conclusions Iron-induced oxidative stress in endometriosis may exceed bilirubin-dependent antioxidant capability, while redox homeostasis in EAOC can be maintained by at least bilirubin.

scholarly journals Reversal of age-associated oxidative stress in mice by PFT, a novel kefir product

2020 ◽  
Vol 34 ◽  
pp. 205873842095014
Author(s):  
Mamdooh Ghoneum ◽  
Shaymaa Abdulmalek ◽  
Deyu Pan
Keyword(s):  
Oxidative Stress ◽  
Low Density Lipoprotein ◽  
Redox Homeostasis ◽  
Density Lipoprotein ◽  
Antioxidant Enzyme Activities ◽  
Protective Effects ◽  
Oxidative Stress Biomarkers ◽  
Age Related ◽  
Total Antioxidant ◽  
The Brain

Introduction: Oxidative stress is a key contributor to aging and age-related diseases. In the present study, we examine the protective effects of PFT, a novel kefir product, against age-associated oxidative stress using aged (10-month-old) mice. Methods: Mice were treated with PFT orally at a daily dose of 2 mg/kg body weight over 6 weeks, and antioxidant status, protein oxidation, and lipid peroxidation were studied in the brain, liver, and blood. Results: PFT supplementation significantly reduced the oxidative stress biomarkers malondialdehyde (MDA) and nitric oxide; reversed the reductions in glutathione (GSH) levels, total antioxidant capacity (TAC), and anti-hydroxyl radical (AHR) content; enhanced the antioxidant enzyme activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD); inhibited the liver enzyme levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT); significantly reduced triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels; and significantly elevated high density lipoprotein (HDL) levels. Interestingly, PFT supplementation reversed the oxidative changes associated with aging, thus bringing levels to within the limits of the young control mice in the brain, liver, and blood. We also note that PFT affects the redox homeostasis of young mice and that it is corrected post-treatment with PFT. Conclusion: Our findings show the effectiveness of dietary PFT supplementation in modulating age-associated oxidative stress in mice and motivate further studies of PFT’s effects in reducing age-associated disorders where free radicals and oxidative stress are the major cause.

scholarly journals Strigolactone GR24 upregulates Nrf2 target genes and may protect against oxidative stress in skeletal muscle

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1459
Author(s):  
Shalem Raju Modi ◽  
Tarja Kokkola
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factor ◽  
Stress Responses ◽  
Mycorrhizal Fungi ◽  
Target Genes ◽  
Redox Homeostasis ◽  
Antioxidant Defences ◽  
Microarray Gene Expression

GR24 is a synthetic strigolactone analog, demonstrated to regulate the development of plants and arbuscular mycorrhizal fungi. GR24 possesses anti-cancer and anti-apoptotic properties, enhances insulin sensitivity and mitochondrial biogenesis in skeletal myotubes, inhibits adipogenesis, decreases inflammation in adipocytes and macrophages and downregulates the expression of hepatic gluconeogenic enzymes. Transcription factor Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) is a master regulator of antioxidant response, regulating a multitude of genes involved in cellular stress responses and anti-inflammatory pathways, thus maintaining cellular redox homeostasis. Nrf2 activation reduces the deleterious effects of mitochondrial toxins and has multiple roles in promoting mitochondrial function and dynamics. We studied the role of GR24 on gene expression in rat L6 skeletal muscle cells which were differentiated into myotubes. The myotubes were treated with GR24 and analyzed by microarray gene expression profiling. GR24 upregulated the cytoprotective transcription factor Nrf2 and its target genes, activating antioxidant defences, suggesting that GR24 may protect skeletal muscle from the toxic effects of oxidative stress.

scholarly journals ATM inhibition enhances Auranofin-induced oxidative stress and cell death in lung cell lines

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244060
Author(s):  
Vanessa Ehrenfeld ◽  
Jan R. Heusel ◽  
Simone Fulda ◽  
Sjoerd J. L. van Wijk
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Ataxia Telangiectasia ◽  
Redox Homeostasis ◽  
Thioredoxin Reductase ◽  
Redox Balance ◽  
Lung Cells ◽  
Chromosomal Breakage ◽  
Atm Kinase ◽  
Cellular Reactive Oxygen Species

Ataxia-Telangiectasia (A-T), a pleiotropic chromosomal breakage syndrome, is caused by the loss of the kinase Ataxia-telangiectasia mutated (ATM). ATM is not only involved in the response to DNA damage, but also in sensing and counteracting oxidative stress. Since a disturbed redox balance has been implicated in the pathophysiology of A-T lung disease, we aimed to further explore the interplay between ATM and oxidative stress in lung cells. Using a kinetic trapping approach, we could demonstrate an interaction between the trapping mutant TRX1-CS and ATM upon oxidative stress. We could further show that combined inhibition of thioredoxin reductase (TrxR) and ATM kinase activity, using Auranofin and KU55933 respectively, induced an increase in cellular reactive oxygen species (ROS) levels and protein oxidation in lung cells. Furthermore, ATM inhibition sensitized lung cells to Auranofin-induced cell death that could be rescued by ROS scavengers. As a consequence, targeted reduction of ATM by TRX1 could serve as a regulator of oxidative ATM activation and contribute to the maintenance of the cellular redox homeostasis. These results highlight the importance of the redox-active function of ATM in preventing ROS accumulation and cell death in lung cells.

scholarly journals Aging Brain: Prevention of Oxidative Stress by Vitamin E and Exercise

2009 ◽  
Vol 9 ◽  
pp. 366-372 ◽  
Author(s):  
Sambe Asha Devi
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Cognitive Decline ◽  
Middle Age ◽  
Neuronal Loss ◽  
Aging Brain ◽  
Key Factors ◽  
Esterase Inhibitors ◽  
The Brain ◽  
And Oxidative Stress

With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years. A few studies have also suggested that exercise is analogous to acetylcholine esterase inhibitors that are also used extensively to treat cognitive impairment and dementia in Alzheimer's disease. In addition, reports also support that vitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.

scholarly journals Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 235 ◽  
Author(s):  
Surai ◽  
Kochish ◽  
Fisinin ◽  
Kidd
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Vitamin E ◽  
Heat Shock ◽  
Redox Balance ◽  
The Body ◽  
Heme Oxygenase 1 ◽  
Antioxidant Defence ◽  
Antioxidant Defences ◽  
And Oxidative Stress

Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.

scholarly journals Parkinson Disease-Linked Parkin Mediates Redox Reactions That Lower Oxidative Stress In Mammalian Brain

2020 ◽  
Author(s):  
Daniel N. El Kodsi ◽  
Jacqueline M. Tokarew ◽  
Rajib Sengupta ◽  
Nathalie A. Lengacher ◽  
Andy C. Ng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reductase Activity ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Oxidative Modification ◽  
Reduced Form ◽  
Mammalian Brain ◽  
Anti Oxidant

SUMMARYWe recently hypothesized that parkin plays a role in redox homeostasis and provided evidence that it directly reduces hydrogen peroxide (H2O2) in vitro. Here, we examined this anti-oxidant activity in vivo. Informed by findings in human brain, we demonstrate that elevated oxidative stress promotes parkin insolubility in mice. In normal mouse brain parkin was partially oxidized, e.g., at cysteines 195 and 252, which was augmented by oxidative stress. Although under basal conditions H2O2 levels were unchanged in adult prkn-/- brain, a parkin-dependent reduction of cytosolic H2O2 was observed when mitochondria were impaired, either due to neurotoxicant exposure (MPTP) or Sod2 haploinsufficiency. In accordance, markers of oxidative stress, e.g., protein carbonylation and nitrotyrosination, were elevated in the cytosol but not in mitochondria from prkn-/- mice. Nevertheless, this rise in oxidative stress led to changes in mitochondrial enzyme activities and the metabolism of glutathione in cells and mammalian brain. In parkin’s absence reduced glutathione concentrations were increased including in human cortex. This compensation was not due to new glutathione synthesis but attributed to elevated oxidized glutathione (GSSG)-reductase activity. Moreover, we discovered that parkin also recycled GSSG to its reduced form. With this reaction, parkin became S-glutathionylated, e.g., at cysteines 59 and human-specific 95. This oxidative modification was reversed by glutaredoxin. Our results demonstrate that cytosolic parkin mediates anti-oxidant reactions including H2O2 reduction and glutathione regeneration. These reducing activities lead to a range of oxidative modifications in parkin itself. In parkin-deficient brain oxidative stress rises despite changes to maintain redox balance.

scholarly journals Alteration on redox status in saliva of microcephaly children

2021 ◽  
Vol 10 (7) ◽  
pp. e40010716796
Author(s):  
Thayane Miranda Alves ◽  
Cintia Megid Barbieri ◽  
Marco Aurelio Gomes ◽  
Heitor Ceolin Araujo ◽  
Nathália de Oliveira Visquette ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurological Disorders ◽  
Redox Balance ◽  
Redox Status ◽  
Antioxidant Defenses ◽  
Frap Assay ◽  
Reducing Ability ◽  
Anticonvulsant Medication ◽  
Total Antioxidant ◽  
The Brain

Microcephaly is described as a reduction of the head circumference, due to the premature fusion of the bones of the skull, preventing the brain from growing normally and reaching its maximum development. This condition may result in neurological disorders, phonation and chewing dysfunction, dysphagia and risk of malnutrition. This alteration contributes to oral hygiene impairment, and continuous uses of the antipsychotic and anticonvulsant medication. Thus, the purpose of this study was to evaluate if microcephaly modified redox balance in saliva. Our hypothesis is that in the microcephalic patient's salivary oxidative stress is lower because of the increase in antioxidant defenses. The study included 13 patients with microcephaly (microcephalic group – MC) and 12 patients without neurological disorders (normocephalic group – NC), from zero to ten years old, no edentulous. Saliva was collected using a cotton wool swab, placing it on the child's mouth floor. After centrifugation, supernatants were fractionated and stored at -80 °C for analyses. Lipid oxidative was evaluated by TBARS methods, total antioxidant capacity by the ferric reducing ability (FRAP) assay, uric acid (UA) was quantified by modified Trinder reaction, and superoxide dismutase activity (SOD) by inhibition of the pyrogallol auto-oxidation. Total protein was measured using the method of Lowry.  Compared to NC group, TBARS was significantly lower in MC group, while FRAP, UA and SOD were higher. Our hypothesis was confirmed. MC patients have lower salivary oxidative stress, due to increased oxidant defenses.

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