scholarly journals Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

2021 ◽  
Vol 11 (8) ◽  
pp. 693
Author(s):  
Corina Daniela Ene ◽  
Simona Roxana Georgescu ◽  
Mircea Tampa ◽  
Clara Matei ◽  
Cristina Iulia Mitran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lupus Nephritis ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Control Group ◽  
Dna Repair Mechanisms ◽  
Glycation End Products ◽  
Repair Mechanisms ◽  
Low Levels ◽  
Defective Dna Repair

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

scholarly journals MO076REGULATION OF DIFFERENTIAL CELLULAR RESPONSE TO OXIDATIVE STIMULI IN SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Corina-Daniela Ene ◽  
Mircea Penescu ◽  
Simona Roxana Georgescu ◽  
Mircea Tampa ◽  
Ilinca Nicolae
Keyword(s):  
Oxidative Stress ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Cellular Response ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Activity Index ◽  
Group Versus ◽  
Control Group ◽  
Systemic Lupus

Abstract Background and Aims Interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydro carbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Method Our study included 82 volunteers with SLE: 38 SLE volunteers with lupus nephritis (LN group) and 44 SLE volunteers without renal impairment (non-LN group) and a control group of 40 healthy volunteers. LN was diagnosed by histological exam (optic microscopy, electronic microscopy and immunofluorescence). Disease activity was measured by systemic SLE disease activity index (SLEDAI), urinary protein/creatinine ration, anti-dsDNA, C3, C4 and urinary β2-microglobulin. In the present paper, we evaluated in serum: Results We detected high lipid peroxidation, elevated oxidative DNA damage, excess accumulation of reactive carbonylic compounds, important oxidation of carbohydrates, disulphide bonds formation and high nitrotyrosination with statistically significant differences between groups, when compared LN and non-LN groups with control group. When compared LN and non-LN groups, our results showed: 3-Nitrotyrosine levels, the decrease of total and native serum thiols, pentosidine levels, sRAGE level and OGG1 activity correlated with disease activity markers in both LN and non-LN groups, while AGE correlated with disease activity only in non-LN group. Conclusion The cellular response to oxidative stimuli in SLE is concreted in the amplification of oxidative degradation of lipids, proteins, nucleic acid, hydro carbonates and in alteration of endogenous strategies for suppression /modulating oxidative stress. The defective DNA repair mechanism via OGG1 and the reduced regulatory effect of sRAGE in activation AGE-RAGE axis in LN group versus non-LN could explain alteration of renal architecture and development of renal injury.

scholarly journals DNA Damage and Its Cellular Response in Mother and Fetus Exposed to Hyperglycemic Environment

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jusciele Brogin Moreli ◽  
Janine Hertzog Santos ◽  
Clarissa Ribeiro Rocha ◽  
Débora Cristina Damasceno ◽  
Glilciane Morceli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Cellular Response ◽  
Genetic Material ◽  
Endogenous Factors ◽  
Dna Repair Mechanisms ◽  
Scavenging Capacity ◽  
Repair Mechanisms ◽  
The Impact

The increased production of reactive oxygen species (ROS) plays a key role in pathogenesis of diabetic complications. ROS are generated by exogenous and endogenous factors such as during hyperglycemia. When ROS production exceeds the detoxification and scavenging capacity of the cell, oxidative stress ensues. Oxidative stress induces DNA damage and when DNA damage exceeds the cellular capacity to repair it, the accumulation of errors can overwhelm the cell resulting in cell death or fixation of genome mutations that can be transmitted to future cell generations. These mutations can lead to and/or play a role in cancer development. This review aims at (i) understanding the types and consequences of DNA damage during hyperglycemic pregnancy; (ii) identifying the biological role of DNA repair during pregnancy, and (iii) proposing clinical interventions to maintain genome integrity. While hyperglycemia can damage the maternal genetic material, the impact of hyperglycemia on fetal cells is still unclear. DNA repair mechanisms may be important to prevent the deleterious effects of hyperglycemia both in mother and in fetus DNA and, as such, prevent the development of diseases in adulthood. Hence, in clinical practice, maternal glycemic control may represent an important point of intervention to prevent the deleterious effects of maternal hyperglycemia to DNA.

Aging and oxidative stress alter DNA repair mechanisms in male germ cells of superoxide dismutase-1 null mice

2021 ◽  
Author(s):  
Paulina Nguyen-Powanda ◽  
Bernard Robaire
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Superoxide Dismutase ◽  
Germ Cells ◽  
Superoxide Dismutase 1 ◽  
Male Germ Cells ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
And Oxidative Stress

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.

scholarly journals Diquat Determines a Deregulation of lncRNA and mRNA Expression in the Liver of Postweaned Piglets

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jin Wang ◽  
Zhi-xin Li ◽  
Dan-dan Yang ◽  
Pei-qi Liu ◽  
Zhi-qiang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Performance ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Reduction Process ◽  
Future Research ◽  
Control Group ◽  
Oxidoreductase Activity ◽  
Go Terms ◽  
Porcine Hepatocytes

Oxidative stress is detrimental to animals and can depress the growth performance and regulate the gene expression of animals. However, it remains unclear how oxidative stress regulates the expression of long noncoding RNAs (lncRNAs) and mRNAs. Therefore, the purpose of this article was to explore the profiles of lncRNAs and mRNAs in the liver of piglets under oxidative stress. Here, we constructed a piglet oxidative stress model induced by diquat and evaluated the effects of oxidative stress on the growth performance and antioxidant enzyme activity of piglets. We also used RNA-Seq to examine the global expression of lncRNAs and mRNAs in piglets under oxidative stress. The targets of lncRNAs and mRNAs were enriched in gene ontology (GO) terms and signaling pathways. The results show that the growth performance and activities of antioxidant enzymes were decreased in piglets under oxidative stress. Moreover, eight lncRNAs (6 upregulated and 2 downregulated) and 30 mRNAs (8 upregulated and 22 downregulated) were differentially expressed in the oxidative stress group of piglets compared to the negative control group. According to biological processes in enriched GO terms, the oxoacid metabolic process, intramolecular oxidoreductase activity, and oxidation-reduction process play important roles in oxidative stress. Pathway analysis showed that the signaling pathways involved in insulin and glucose metabolism had a close relationship with oxidative stress. Furtherin vitroexperiments showed that the expression of the upregulated geneGNMTwas significantly increased in primary porcine hepatocytes after diquat stimulation. In contrast, the level of the downregulated geneGCKwas significantly decreased at 12 h in primary porcine hepatocytes after diquat stimulation. Our results expand our knowledge of the lncRNAs and mRNAs transcribed in the livers of piglets under oxidative stress and provide a basis for future research on the molecular mechanisms mediating oxidative stress and tissue damage.

scholarly journals Evaluation of radical scavenging system in amoeba Chaos carolinense during nutrient deprivation

2017 ◽  
Vol 7 (4) ◽  
pp. 20160113 ◽  
Author(s):  
Yuru Deng ◽  
Edlyn Li-Hui Lee ◽  
Ketpin Chong ◽  
Zakaria A. Almsherqi
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Nucleic Acids ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Cellular Responses ◽  
Biological Macromolecules

The frequent appearance of non-lamellar membrane arrangements such as cubic membranes (CMs) in cells under stressed or pathological conditions points to an intrinsic cellular response mechanism. CM represents highly curved, three-dimensional nano-periodic structures that correspond to mathematically well-defined triply periodic minimal surfaces. Specifically, cellular membrane may transform into CM organization in response to pathological, inflammatory and oxidative stress conditions. CM organization, thus, may provide an advantage to cope with various types of stress. The identification of inducible membrane systems, such as in the mitochondrial inner membranes to cubic morphology upon starvation, opens new avenues for understanding the molecular mechanisms of cellular responses to oxidative stress. In this study, we compared the cellular responses of starved and fed amoeba Chaos carolinense to oxidative stress. Food deprivation from C. carolinense induces a significant increase in prooxidants such as superoxide and hydrogen peroxide. Surprisingly, we observed a significant lower rate of biomolecular damage in starved cells (with higher free radicals generation) when compared with fed cells. Specifically, lipid and RNA damages were significantly less in starved cells compared with fed cells. This observation was not due to the upregulation of intracellular antioxidants, as starved amoeba show reduced antioxidant enzymatic activities; however, it could be attributed to CM formation. CM could uptake and retain short segments of nucleic acids (resembles cellular RNA) in vivo and in vitro. Previous results showed that nucleic acids retained within CM sustain a minimal oxidative damage in vitro upon exposure to high level of superoxide. We thus propose that CM may act as a ‘protective’ shelter to minimize the oxidation of biologically essential macromolecules such as RNA. In summary, we examined enzymatic antioxidant activities as well as oxidative damage biomarkers in starved amoeba C. carolinense in correlation with the potential role of CM as an optimal intracellular membrane organization for the protection of biological macromolecules against oxidative damage.

scholarly journals Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes

2008 ◽  
Vol 30 (3) ◽  
pp. 243-245 ◽  
Author(s):  
Flávio Kapczinski ◽  
Benício N Frey ◽  
Ana C Andreazza ◽  
Márcia Kauer-Sant'Anna ◽  
Ângelo B M Cunha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bipolar Disorder ◽  
Neurotrophic Factor ◽  
Thiobarbituric Acid ◽  
Brain Derived Neurotrophic Factor ◽  
Oxidative Status ◽  
Control Group ◽  
Healthy Controls ◽  
Thiobarbituric Acid Reactive Substances ◽  
Low Levels

OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.

scholarly journals Cancer Stem Cells and Radioresistance: DNA Repair and Beyond

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 862 ◽  
Author(s):  
Alexander Schulz ◽  
Felix Meyer ◽  
Anna Dubrovska ◽  
Kerstin Borgmann
Keyword(s):  
Stem Cells ◽  
Dna Repair ◽  
Cancer Stem Cells ◽  
Radiation Oncology ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Clinical Findings ◽  
Cell Reprogramming ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms

The current preclinical and clinical findings demonstrate that, in addition to the conventional clinical and pathological indicators that have a prognostic value in radiation oncology, the number of cancer stem cells (CSCs) and their inherent radioresistance are important parameters for local control after radiotherapy. In this review, we discuss the molecular mechanisms of CSC radioresistance attributable to DNA repair mechanisms and the development of CSC-targeted therapies for tumor radiosensitization. We also discuss the current challenges in preclinical and translational CSC research including the high inter- and intratumoral heterogeneity, plasticity of CSCs, and microenvironment-stimulated tumor cell reprogramming.

scholarly journals Chlorella Vulgaris Biomass Supplementation Increased the Abundance of Hepatic Antioxidant Proteins in Relation to Oxidative Stress Reduction in Rabbits

2020 ◽  
Author(s):  
Akeem Babatunde Sikiru ◽  
Arangasamy Arunachalam ◽  
Stephen Sunday Acheneje Egena ◽  
Sejian Veerasamy ◽  
Ippala Janardhan Reddy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chlorella Vulgaris ◽  
Molecular Mechanisms ◽  
Profile Analysis ◽  
Control Group ◽  
Antioxidant Enzyme Activities ◽  
Control Groups ◽  
Antioxidant Genes ◽  
Significant Difference ◽  
Antioxidant Proteins

Abstract Background Chlorella vulgaris is a unicellular microalga that is rich in antioxidant, its supplementation has been reported to reduce oxidative stress via upregulations of antioxidant genes. However, there are scarce reports on its effect on antioxidant protein expressions in rabbits – a situation which necessitate an untargeted proteomic profile analysis due to its supplementation. This is because untargeted proteomics profiling is an approach suitable for assessing the effectiveness of genes code translation into polypeptide chains folded into functional proteins used for specific sub-cellular or extracellular physiological activities. It remains one of the comparative avenues for evaluating the efficacies of drugs and nutraceutical agents including antioxidants. In this study, the antioxidant efficacy of a microalga Chlorella vulgaris was evaluated at molecular levels using its hepatic protein expression in rabbit models. Results After 120 days of the microalga supplementation, protein was extracted from liver of the rabbits for untargeted proteomics profiling using LC-MS/Orbitrap Fusion Tribrid™ peptides quantifier and sequencer. There were five-hundred and eleven (511) proteins identified; and among the proteins, 191 were specific to the control group while 186 were specific to the Treatment group; and 134 were common to both groups. Independent samples t-test of the protein abundance indicated that there was a significant difference (p = 0.01) between the treatment and the control groups. There was also a significant reduction in the malondialdehyde concentrations (p = 0.01), higher total antioxidant capacities (p = 0.002), and increased antioxidant enzyme activities (p = 0.05) between the treatment and control groups.Conclusion The study concluded that one of the molecular mechanisms associated with Chlorella vulgaris intake reduction of the hepatic oxidative stress is increased abundances of antioxidant proteins and reduction of the lipid peroxidation and these led to a suggestion that the microalga is a potent antioxidant agent suitable for protecting against oxidative stress in rabbits and other domestic food producing animals.

scholarly journals RADIATION GENETICS IN MICROORGANISMS AND EVOLUTIONARY CONSIDERATIONS

Genetics ◽  
1974 ◽  
Vol 78 (1) ◽  
pp. 149-161
Author(s):  
Sohei Kondo
Keyword(s):  
Dna Repair ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Resistance Mechanisms ◽  
Plant Viruses ◽  
Protective Capacity ◽  
E Coli ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Solar Uv

ABSTRACT Recent knowledge of UV-resistance mechanisms in microorganisms is reviewed in perspective, with emphasis on E. coli. Dark-repair genes are classified into "excision" and "tolerance" (ability to produce a normal copy of DNA from damaged DNA). The phenotype of DNA repair is rather common among the microorganisms compared, and yet their molecular mechanisms are not universal. In contrast, DNA photoreactivation is the simplest and the most general among these three repair systems. It is proposed that DNA repair mechanisms evolved in the order: photoreactivation, excision repair, and tolerance repair. The UV protective capacity and light-inducible RNA photoreactivation possessed by some plant viruses are interpreted to be the result of solar UV selection during a rather recent era of evolution.

Liability to Chromosome Damage in Lymphocytes of “Cancer Family” Subjects: A Study of Spontaneous and Induced Chromosomal Fragility

1987 ◽  
Vol 2 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Lidia Larizza ◽  
Luisa Doneda ◽  
Miria Stefanini ◽  
Giuseppa Francone ◽  
Valter Gualandri ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Fragile Sites ◽  
Chromosome 1 ◽  
Chromosome Damage ◽  
Tumor Patients ◽  
Dna Repair Mechanisms ◽  
Chromosomal Fragility ◽  
Repair Mechanisms ◽  
Heterochromatin Polymorphism ◽  
Defective Dna Repair

Spontaneous chromosomal fragility was detected in seven tumor patients and one healthy member from two families with a high recurrence of cancer. Major chromosome lesions, such as terminal deletions and rearranged chromosomes, were found at levels significantly higher than those reported for control individuals. The prevalence of these aberrations in comparison to minor ones (chromosome gaps and chromatid breaks) in this group ofpatients seems to indicate that the fragility observed is the end-point of a process of chromosomal instability, which may have already been brought to expression. Study of other parameters of genetic instability in the most unstable karyotypes showed that the chromosome damage observed was neither paralleled by abnormal SCE frequency nor sustained by defective DNA repair mechanisms or expression of inherited or constitutional fragile sites. As all the subjects investigated here had previously been shown to display intraindividual variations in the C-banded region of chromosome 1, it is possible that spontaneous fragility and acquired C-heterochromatin polymorphism may be markers that, combined with chromosomal instability, create genetic predisposition to cancer.

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