scholarly journals Antioxidant Defense Enzyme Genes and Asthma Susceptibility: Gender-Specific Effects and Heterogeneity in Gene-Gene Interactions between Pathogenetic Variants of the Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Alexey V. Polonikov ◽  
Vladimir P. Ivanov ◽  
Alexey D. Bogomazov ◽  
Maxim B. Freidin ◽  
Thomas Illig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candidate Genes ◽  
Antioxidant Defense ◽  
Nucleotide Polymorphisms ◽  
Asthma Susceptibility ◽  
Specific Effects ◽  
Antioxidant Defense Enzymes ◽  
Genes Encoding ◽  
Antioxidant Defense Enzyme ◽  
Gender Specific

Oxidative stress resulting from an increased amount of reactive oxygen species and an imbalance between oxidants and antioxidants plays an important role in the pathogenesis of asthma. The present study tested the hypothesis that genetic susceptibility to allergic and nonallergic variants of asthma is determined by complex interactions between genes encoding antioxidant defense enzymes (ADE). We carried out a comprehensive analysis of the associations between adult asthma and 46 single nucleotide polymorphisms of 34 ADE genes and 12 other candidate genes of asthma in Russian population using set association analysis and multifactor dimensionality reduction approaches. We found for the first time epistatic interactions between ADE genes underlying asthma susceptibility and the genetic heterogeneity between allergic and nonallergic variants of the disease. We identifiedGSR(glutathione reductase) andPON2(paraoxonase 2) as novel candidate genes for asthma susceptibility. We observed gender-specific effects of ADE genes on the risk of asthma. The results of the study demonstrate complexity and diversity of interactions between genes involved in oxidative stress underlying susceptibility to allergic and nonallergic asthma.

scholarly journals A redox signature score identifies diffuse large B-cell lymphoma patients with a poor prognosis

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3594-3601 ◽  
Author(s):  
Margaret E. Tome ◽  
David B. F. Johnson ◽  
Lisa M. Rimsza ◽  
Robin A. Roberts ◽  
Thomas M. Grogan ◽  
...  
Keyword(s):  
B Cell ◽  
Antioxidant Defense ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Outcome Predictor ◽  
Defense Enzyme ◽  
Large B Cell Lymphoma ◽  
Antioxidant Defense Enzymes ◽  
Antioxidant Defense Enzyme ◽  
Large B Cell

AbstractDiffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease in which approximately 40% of the patients respond well to current chemotherapy, but the prognosis for the other 60% is poor. The Leukemia/Lymphoma Molecular Profiling Project (LLMPP) used microarray technology to define a molecular profile for each of 240 patients with DLBCL and develop a molecular outcome predictor score that accurately predicted patient survival. Data from our laboratory and others suggest that alterations in antioxidant defense enzyme levels and redox environment can be oncogenic and affect the response to glucocorticoid treatment, one of the components of combination chemotherapy regimens for lymphoma. The goal of the current study was to reanalyze the LLMPP microarray data to determine whether the levels of antioxidant defense enzymes and redox proteins were correlated with prognosis in DLBCL. We found that patients with DLBCL with the worst prognosis, according to the outcome predictor score, had decreased expression of catalase, glutathione peroxidase, manganese superoxide dismutase, and VDUP1, a protein that inhibits thioredoxin activity. The data suggest that the patients with the worst prognosis combine a decrease in antioxidant defense enzyme expression with an increase in thioredoxin system function (the redox signature score).

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.

scholarly journals Tagging Single-Nucleotide Polymorphisms in Antioxidant Defense Enzymes and Susceptibility to Breast Cancer

2006 ◽  
Vol 66 (2) ◽  
pp. 1225-1233 ◽  
Author(s):  
Arancha Cebrian ◽  
Paul D. Pharoah ◽  
Shahana Ahmed ◽  
Paula L. Smith ◽  
Craig Luccarini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Antioxidant Defense ◽  
Defense Enzymes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Antioxidant Defense Enzymes

scholarly journals Activities of antioxidant defense enzymes in the blood of individuals with Leu144Phe mutation

2005 ◽  
Vol 24 (2) ◽  
pp. 111-114 ◽  
Author(s):  
Aleksandra Nikolic ◽  
Zorica Stevic ◽  
Dusko Blagojevic ◽  
Zorica Saicic ◽  
Mihajlo Spasic
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Antioxidant Defense ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Defense Enzymes ◽  
Glutathione S Transferase ◽  
Zinc Superoxide Dismutase ◽  
Antioxidant Defense Enzymes ◽  
Discriminant Analyses ◽  
Lateral Sclerosis

Activities of cooper zinc superoxide dismutase (Cu,Zn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) in the blood of familial amyotrophic lateral sclerosis patients with Leu144Phe mutation (FALS), asimptomatic carriers with Leu144Phe mutation and controls were studied. Activity of Cu,Zn SOD was significantly lower in the FALS patients and asimptomatic carriers than in controls (p<0.001). In the FALS patients GSH-Px activity was lower (p<0.01) and activity of GR was higher (p<0.001) in comparison with controls. Canonical discriminant analyses provide statistical evidence that examined groups are different in the composition of antioxidant enzymes in blood and revealed that each component confers to observed difference. Our results suggests that oxidative stress is involved in pathogenesis of FALS and the activities of antioxidant enzymes are exposed to different kind of oxidative pressure in FALS patients, asymptomatic carriers and controls.

scholarly journals Curcumin reduces malondialdehyde and improves antioxidants in humans with diseased conditions: a comprehensive meta-analysis of randomized controlled trials

BioMedicine ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 23 ◽  
Author(s):  
Mohammad Alizadeh ◽  
Sorayya Kheirouri
Keyword(s):  
Oxidative Stress ◽  
Randomized Controlled Trials ◽  
Antioxidant Defense ◽  
Human Subjects ◽  
Meta Analysis ◽  
Research Question ◽  
Control Group ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Antioxidant Defense Enzymes

Objective: This systematic review and meta-analysis was conducted to collate the effects of curcumin on MDA and antioxidant markers in individuals with diseased conditions. In this study the research question was “does curcumin supplementation improves oxidative stress and antioxidant defense enzymes in human subjects compared to a group without curcumin supplementation? Methods: This research included randomized controlled trials published in English in any year, in which intervention with curcumin was compared to either placebo, or standard of care or no intervention. Pubmed, Embase, Cochrane Central, Scopus and Google Scholar were searched. Meta-analysis was performed using RevMan (version 5.3), with standardized mean differences (SMD) and random-effects models. Results: One hundred twenty-seven titles and abstracts were identified which 17 articles were included for final analysis. The number of participants ranged from 22 to 160 across the included studies. The duration of intervention, dose of curcumin and location of outcomes measurements varied across the studies. Curcumin significantly reduced MDA [SMD −0.46 (95% CI: −0.68 to −0.25)] and increased superoxide dismutase (SOD) [0.82 (0.27 to 1.38)], catalase [10.26 (0.92 to 19.61)], and glutathione peroxidase [8.90 (6.62 to 11.19)] when compared with control group. Subgroup analyses displayed that curcumin could significantly reduce MDA levels with or without use of piperine, however it could increase SOD level in presence of piperine. Conclusions: These findings suggest that curcumin may be used as an adjunct therapy in individuals with oxidative stress. The administration of piperine with curcumin may enhance the efficacy of curcumin on antioxidant defense system.

scholarly journals Gene of gamma-glutamylcyclotransferase, a key enzyme of glutathione catabolism, and predisposition to ischemic stroke: association analysis and functional annotation of gene polymorphisms

2020 ◽  
pp. 32-39
Author(s):  
Ю.А. Бочарова ◽  
Ю.Э. Азарова ◽  
Е.Ю. Клёсова ◽  
Е.Л. Дроздова ◽  
М.А. Солодилова ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Annotation ◽  
Gene Polymorphisms ◽  
Disease Risk ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Nucleotide Polymorphisms ◽  
Antioxidant Defense Enzymes ◽  
Genes Encoding ◽  
Key Enzyme

Генетико-эпидемиологическими исследованиями установлено, что полиморфные варианты генов ферментов антиоксидантной системы являются значимыми предикторами риска развития и тяжести проявления ишемического инсульта (ИИ). Целью настоящего исследования было изучение ассоциации трех частых однонуклеотидных полиморфизмов (SNP) rs38420, rs4270 и rs6462210 гена гамма-глутамилциклотрансферазы (GGCT) - ключевого фермента катаболизма глутатиона с риском развития ИИ и функциональное аннотирование этих SNPs. Материалом для исследования послужили образцы ДНК 1288 неродственных индивидов славянского происхождения, в том числе 600 пациентов с диагнозом ИИ и 688 относительно здоровых добровольцев. Генотипирование полиморфных вариантов гена GGCT осуществлялось с использованием технологии iPLEX на генетическом анализаторе MassARRAY-4. Функциональное аннотирование SNPs осуществлялось биоинформатическими методами с использованием различных онлайн-инструментов и баз данных. Установлена ассоциация генотипа TT SNP rs6462210 с пониженным риском развития ишемического инсульта (OR=0,36 95%CI 0,15-0,85, p=0,01). Биоинформатический анализ регуляторного потенциала исследованных полиморфных вариантов показал, что их фенотипические эффекты проявляются ослаблением транскрипционной активности гена GGCT преимущественно в клетках крови и артериях, главным образом, в результате химических модификаций хроматина. У полиморфизма rs4270, находящегося в тесном неравновесии по сцеплению с SNP rs6462210 (D’=0,966, p<0,01), обнаружен участок связывания c микроРНК hsa-miR-1246, способной блокировать экспрессию GGCT, тем самым, способствуя снижению образования L-цистеина - предшественника глутатиона. В результате исследования впервые показано, что вариабельность гена GGCT может вносить вклад в развитие ИИ. Экспериментальные исследования по оценке регуляторного потенциала полиморфных вариантов гена GGCT потребуются для патофизиологической интерпретации выявленных ассоциаций. Genetic epidemiological studies have established that polymorphisms of the genes encoding antioxidant defense enzymes represent meaningful predictors for the risk and severity of ischemic stroke (IS). The aim of this study was to investigate associations of IS with three common single nucleotide polymorphisms (SNPs) such as rs38420, rs4270 and rs6462210 in gamma-glutamylcyclotransferase (GGCT) gene, a key enzyme of glutathione catabolism. DNA samples obtained from 1288 unrelated individuals of Slavic origin, including 600 patients with IS and 688 healthy volunteers were included in the study. Genotyping of the GGCT polymorphisms was done using an iPLEX-based technology by the MassARRAY-4 system. Functional annotation of SNPs was performed using numerous online bioinformatics tools and resources. We found an association between genotype T/T rs6462210 and a decreased risk of ischemic stroke (OR = 0.36 95% CI 0.15-0.85, p=0.01). The haplotype rs38420A-rs4270T-rs6462210C showed a clear tendency in association with decreased disease risk (p=0.057). Bioinformatics analysis showed that the phenotypic effects of the SNPs are characterized by a weak transcriptional activity of the GGCT gene mainly in blood cells and arteries as a result of chemical modifications of chromatin. For the rs4270 polymorphism, which is in close linkage disequilibrium with SNP rs6462210 (D’=0.966, p<0.01), we found a binding site for miRNA hsa-miR-1246 which is capable to block the GGCT expression, thereby reducing the formation of L-cysteine, a precursor of glutathione. The study showed for the first time that GGCT gene may contribute to the development of ischemic stroke. Experimental studies focusing on the regulatory potential of GGCT gene polymorphisms are required for the pathophysiological interpretation of the identified associations.

scholarly journals Catalase C-262T Gene Variant in Patients with Bronchial Asthma

2017 ◽  
Vol 34 (3) ◽  
pp. 205-212
Author(s):  
Milena Despotović ◽  
Tatjana Jevtović Stoimenov ◽  
Ivana Stanković ◽  
Jelena Bašić ◽  
Branka Đorđević ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bronchial Asthma ◽  
Antioxidant Defense ◽  
Chronic Inflammatory Disease ◽  
Recessive Model ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Catalase Gene ◽  
Pcr Rflp

Summary Bronchial asthma (BA) is a chronic inflammatory disease of the airways in the pathogenesis of which oxidative stress has a very important role. Single nucleotide polymorphisms (SNPs) in catalase gene may result in decreased antioxidative defense capacity, and thus a higher risk for BA development. Since oxidative stress has an important role in the pathogenesis of BA and catalase has a key role in antioxidant defense, the aim of this study was to examine the association of CAT C-262T polymorphism with BA in Serbian patients with BA. A total of 170 subjects (79 patients with BA and 91 controls) were screened for CAT C-262T SNP using PCR-RFLP method. The analysis of genotype distribution did not show statistically significant differences between BA patients and controls (p > 0.05). Moreover, no differences were detected when comparison was performed based on dominant or recessive model. The distribution of CAT-262C and CAT-262T alleles did not show differences between patients and healthy controls (p = 0.715; OR = 1.091; 95% CI = 0.684–1.741). Further analysis of genotype and allele distributions, based on stratification by sex, did not show significant differences between BA patients and controls (p > 0.05). This is the first study that examined CAT C-262T (rs1001179) SNP in Serbian patients with BA. The results obtained in this study showed that biallelic SNP at the position-262 in the catalase gene is not associated with BA in the Serbian population.

scholarly journals Pseudoxanthoma Elasticum: Genetic Variations in Antioxidant Genes Are Risk Factors for Early Disease Onset

2007 ◽  
Vol 53 (10) ◽  
pp. 1734-1740 ◽  
Author(s):  
Ralf Zarbock ◽  
Doris Hendig ◽  
Christiane Szliska ◽  
Knut Kleesiek ◽  
Christian Götting
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Disease Onset ◽  
Cumulative Effect ◽  
Pseudoxanthoma Elasticum ◽  
Elastic Fibers ◽  
Nucleotide Polymorphisms ◽  
Antioxidant Genes ◽  
Specific Pcr ◽  
Genes Encoding

Abstract Background: Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder characterized by progressive calcification and fragmentation of elastic fibers in connective tissues. PXE is caused by mutations in the ABCC6 gene, which encodes the membrane transporter multidrug resistance–associated protein 6. Chronic oxidative stress was recently suggested to play a crucial role in the pathogenesis of the disease. Our aim was to investigate the association of PXE with genetic variation in genes coding for antioxidant enzymes. Methods: We used restriction fragment length polymorphism and allele-specific PCR analyses to evaluate the distribution of single-nucleotide polymorphisms in the genes encoding catalase (CAT), superoxide dismutase 2 (SOD2), and glutathione peroxidase 1 (GPX1) in DNA samples from 117 German PXE patients and 117 healthy age- and sex-matched control individuals. Results: The investigated genetic variants had previously been shown to affect the activities of these antioxidant enzymes. We found a correlation between genotype and age of disease onset for polymorphisms in CAT (c.−262C&gt;T), SOD2 (c.47C&gt;T), and GPX1 (c.593C&gt;T). Furthermore, the age of disease onset was inversely correlated with the number of mutated alleles, indicating a cumulative effect on the time of disease onset [mean (SD) age of 40.9 (13.6) years, 32.4 (16.3) years, and 25.7 (15.9) years for carriers of 0, 1–2, and &gt;2 mutated alleles, respectively; P = 0.03]. Conclusion: Our findings demonstrate that increased oxidative stress due to activity-affecting polymorphisms in genes encoding antioxidant enzymes leads to earlier PXE onset.

scholarly journals Protective Effects of Sulforaphane on Exercise-Induced Organ Damage via Inducing Antioxidant Defense Responses

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 136 ◽  
Author(s):  
Ruheea Taskin Ruhee ◽  
Sihui Ma ◽  
Katsuhiko Suzuki
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Antioxidant Defense ◽  
Defense Responses ◽  
Organ Damage ◽  
Exercise Group ◽  
Exhaustive Exercise ◽  
Protective Effects ◽  
Antioxidant Defense Enzymes ◽  
Exercise Induced

Regular exercise is beneficial to maintain a healthy lifestyle, but the beneficial effects are lost in the case of acute exhaustive exercise; this causes significant inflammation, oxidative stress along with organ damage. Recently, sulforaphane (SFN), an indirect antioxidant, has drawn special attention for its potential protective effect against inflammation and oxidative stress. However, no studies have been performed regarding acute exhaustive exercise-induced organ damage in association with SFN administration. Therefore, the aim of this study was to investigate the effects of SFN on acute exhaustive exercise-induced organ damage and the mechanisms involved. To perform the study, we divided mice into four groups: Control, SFN, exercise, and SFN plus exercise. The SFN group was administered orally (50 mg/kg body wt) 2 h before the running test. We measured plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), and acute exhaustive exercise significantly increased these biomarkers. In addition, the mRNA expression of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α, were significantly increased in the liver of exercise group. However, the SFN plus exercise group showed a significant reduction in the expression of cytokines and blood biomarkers of tissue damage or cell death. Furthermore, we measured mRNA expression of Nrf2, heme oxygenase (HO)-1, and antioxidant defense enzymes expression, i.e., superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPx1) in the liver. The expression of all these biomarkers was significantly upregulated in the SFN plus exercise group. Collectively, SFN may protect the liver from exhaustive exercise-induced inflammation via inducing antioxidant defense response through the activation of Nrf2/HO-1 signal transduction pathway.

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