Curcumin Resuscitate Gliadin Induced Oxidative Damage And Altered Cellular Responses In Human Intestinal Cells Via Cross-Talk Between The Transcription Factor Nrf-2 And Multifunctional Protein APE1

2021 ◽  
Author(s):  
Kunj Bihari Gupta ◽  
Anil Kumar Mantha ◽  
Monisha Dhiman
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Nitrosative Stress ◽  
Mitochondrial Ros ◽  
Hct 116 ◽  
Wheat Gliadin ◽  
Pre Treatment ◽  
Gliadin Protein ◽  
Ht 29

Abstract An imbalance between the production of oxygen and nitrogen free radicals and their degradation by the antioxidant system are the major causative factors for the wheat intolerance diseases. In the present study, we have examined the wheat gliadin protein-induced oxidative and nitrosative stress and downstream responses in the human intestinal cell lines viz. HCT-116 and HT-29. The role of phytochemical curcumin was investigated to alleviate the gliadin associated cellular damages. The focus of the study was to identify the role of key DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) in gliadin protein-induced toxicity in the intestine, which may be crucial for establishing the gut-associated diseases. Reactive oxygen species (ROS); reactive nitrogen species (RNS); mitochondrial ROS; mitochondrial trans-membrane potential; protein carbonylation; lipid peroxidation; and the oxidized DNA base damage was estimated in HCT-116 and HT-29 cells after 24 h treatment of 160 µg/ml of gliadin, 10 µM of curcumin and its combination. In addition, the transcriptional expression and enzymatic activities of antioxidants (SOD; Catalase; and GSH) were measured in the in these cells. Furthermore, the cross-talk between the nuclear factor erythroid 2-related factor-2 (Nrf-2) and the multifunctional enzyme APE1 was analyzed by the immunofluorescent based imaging and co-immunoprecipitation assays. The endonuclease activity of APE1 and the DNA-protein interaction of NRF-2 with ARE was analyzed by using electrophoretic mobility shift assay (EMSA) with the nuclear lysates of HCT-116 and HT-29 cells. Results suggest that 3 h pre-treatment of curcumin followed by the treatment of gliadin protein for 24 h time protect the HCT-116 and HT-29 cells via (1) decreasing the ROS, RNS, oxidative stress, mitochondrial ROS, recuperate mitochondrial trans-membrane potential; (2) reestablishing the cellular antioxidant defence systems; (3) enhancing the DNA-repair via APE1 and which further activates the ARE elements via activation of Nrf-2. In conclusion, wheat gliadin induces the oxidative/nitrosative stress, mitochondrial damage and damages the cellular biomolecules; hence is associated with the disease pathogenesis and tissue damage in wheat intolerance diseases. The gliadin induced stress and its consequences are significantly reduced by the pre-treatment of curcumin via DNA repair pathways and oxidative stress which is evident through the interaction between two essential proteins of these pathways APE1 and Nrf-2 hence suggesting the role of curcumin based management of wheat intolerance diseases like celiac disease.

scholarly journals The role of oxidative and nitrosative stress in the pathology of osteoarthritis: Novel candidate biomarkers for quantification of degenerative changes in the knee joint

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Alexander Franz ◽  
Laura Joseph ◽  
Constantin Mayer ◽  
Jan-Frieder Harmsen ◽  
Holger Schrumpf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Fluid ◽  
Knee Joint ◽  
Human Serum ◽  
Synovial Membrane ◽  
Nitrosative Stress ◽  
Control Groups ◽  
Oxidative And Nitrosative Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.

scholarly journals Associations Between Polymorphisms in Genes Related to Oxidative Stress and DNA Repair, Interactions With Serum Antioxidants, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

2022 ◽  
Vol 11 ◽  
Author(s):  
Zhihong Gong ◽  
Mary E. Platek ◽  
Cathee Till ◽  
Phyllis J. Goodman ◽  
Catherine M. Tangen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Prevention ◽  
Prostate Cancer Risk ◽  
Minor Allele ◽  
Cancer Etiology ◽  
Lower Serum ◽  
Prostate Cancer Prevention

Study of polymorphisms in genes related to the generation and removal of oxidative stress and repair of oxidative DNA damage will lead to new insights into the genetic basis of prostate cancer. In the Prostate Cancer Prevention Trial (PCPT), a double-blind, randomized controlled trial testing finasteride versus placebo for prostate cancer prevention, we intend to investigate the role of oxidative stress/DNA repair mechanisms in prostate cancer etiology and whether these polymorphisms modify prostate cancer risk by interacting with antioxidant status in both placebo and finasteride arms. We evaluated associations of selected candidate polymorphisms in genes in these pathways, and interactions with pre-diagnostic serum antioxidants, and the risk of prostate cancer among 1,598 cases and 1,706 frequency-matched controls enrolled in the PCPT. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. While there were no statistically significant associations observed in the placebo arm, several SNPs were associated with prostate cancer in the finasteride arm. Specifically, APEX1-rs1760944 was associated with increased risk of total prostate cancer (per minor allele: p-trend=0.04). OGG1-rs1052133 was positively (CG/GG vs. CC: OR=1.32, 95% CI: 1.01-1.73) and NOS3-rs1799983 was inversely (per minor allele: p-trend=0.04) associated with risk of low-grade prostate cancer. LIG3-rs1052536 and XRCC1-rs25489 were suggestively associated with reduced risk of high-grade prostate cancer (per minor allele: both p-trend=0.04). In the placebo arm, significant associations were observed among men with higher serum lycopene for APEX1-rs1760944 and NQO1-rs1800566, or higher serum β-cryptoxanthin for ERCC4-rs1800067. In the finasteride arm, stronger associations were observed among men with lower serum lycopene for NOS3-rs1799983, higher serum α-carotene, β-carotene, and β-cryptoxanthin for LIG3-rs1052536, or lower serum retinol for SOD2-rs1799725. These results suggest that germline variations in oxidative stress and DNA repair pathways may contribute to prostate carcinogenesis and that these associations may differ by intraprostatic sex steroid hormone status and be further modified by antioxidant status. Findings provide insights into the complex role of gene, gene-antioxidant and -finasteride interactions in prostate cancer etiology, and thus may lead to the development of preventative strategies.

scholarly journals Roles of Autophagy in Oxidative Stress

2020 ◽  
Vol 21 (9) ◽  
pp. 3289 ◽  
Author(s):  
Hyeong Rok Yun ◽  
Yong Hwa Jo ◽  
Jieun Kim ◽  
Yoonhwa Shin ◽  
Sung Soo Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Stress Responses ◽  
Basic Mechanism ◽  
Redox Signalling ◽  
Mitochondrial Ros ◽  
Related Stress ◽  
And Function ◽  
Catabolic Process

Autophagy is a catabolic process for unnecessary or dysfunctional cytoplasmic contents by lysosomal degradation pathways. Autophagy is implicated in various biological processes such as programmed cell death, stress responses, elimination of damaged organelles and development. The role of autophagy as a crucial mediator has been clarified and expanded in the pathological response to redox signalling. Autophagy is a major sensor of the redox signalling. Reactive oxygen species (ROS) are highly reactive molecules that are generated as by-products of cellular metabolism, principally by mitochondria. Mitochondrial ROS (mROS) are beneficial or detrimental to cells depending on their concentration and location. mROS function as redox messengers in intracellular signalling at physiologically low level, whereas excessive production of mROS causes oxidative damage to cellular constituents and thus incurs cell death. Hence, the balance of autophagy-related stress adaptation and cell death is important to comprehend redox signalling-related pathogenesis. In this review, we attempt to provide an overview the basic mechanism and function of autophagy in the context of response to oxidative stress and redox signalling in pathology.

scholarly journals Microbiological-Chemical Sourced Chondroitin Sulfates Protect Neuroblastoma SH-SY5Y Cells against Oxidative Stress and Are Suitable for Hydrogel-Based Controlled Release

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1816
Author(s):  
Emiliano Bedini ◽  
Alfonso Iadonisi ◽  
Chiara Schiraldi ◽  
Laura Colombo ◽  
Diego Albani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuroprotective Effect ◽  
Polymer Networks ◽  
Interpenetrating Polymer Networks ◽  
Ethical Concerns ◽  
Chondroitin Sulfates ◽  
Sulfation Pattern ◽  
Pre Treatment ◽  
Set Up

Chondroitin sulfates (CS) are a class of sulfated glycosaminoglycans involved in many biological processes. Several studies reported their protective effect against neurodegenerative conditions like Alzheimer’s disease. CS are commonly derived from animal sources, but ethical concerns, the risk of contamination with animal proteins, and the difficulty in controlling the sulfation pattern have prompted research towards non-animal sources. Here we exploited two microbiological-chemical sourced CS (i.e., CS-A,C and CS-A,C,K,L) and Carbopol 974P NF/agarose semi-interpenetrating polymer networks (i.e., P.NaOH.0 and P.Ethanol.0) to set up a release system, and tested the neuroprotective role of released CS against H2O2-induced oxidative stress. After assessing that our CS (1–100 µM) require a 3 h pre-treatment for neuroprotection with SH-SY5Y cells, we evaluated whether the autoclave type (i.e., N- or B-type) affects hydrogel viscoelastic properties. We selected B-type autoclaves and repeated the study after loading CS (1 or 0.1 mg CS/0.5 mL gel). After loading 1 mg CS/0.5 mL gel, we evaluated CS release up to 7 days by 1,9-dimethylmethylene blue (DMMB) assay and verified the neuroprotective role of CS-A,C (1 µM) in the supernatants. We observed that CS-A,C exhibits a broader neuroprotective effect than CS-A,C,K,L. Moreover, sulfation pattern affects not only neuroprotection, but also drug release.

P6279Mitochondria targeted catalase overexpression protects against beta-adrenergic receptor mediated cardiac remodeling in mice

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Uribe ◽  
D Andersson
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Adrenergic Receptor ◽  
Weight Ratio ◽  
Receptor Activation ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Mitochondrial Ros ◽  
Beta Adrenergic Agonist

Abstract Background Beta-adrenergic receptor signaling is widely recognized as a fundamental component in the pathogenesis of chronic heart failure. However, the mechanisms behind beta-adrenergic receptor-mediated remodeling in cardiomyocytes and the myocardium are not fully understood. Oxidative stress has been proposed as a central pathophysiological mediator in cardiovascular disease and heart failure. The triggers and sources of oxidative stress in heart failure remain unclear. In this study we use mice with mitochondria-targeted overexpression of the antioxidant enzyme catalase (mCAT) to link beta-adrenergic receptor-mediated stress to mitochondrial reactive oxidative species (ROS) and the progression of heart failure. Hypothesis Mitochondrial ROS, induced by beta-adrenergic receptor-activation, is a mediator in the progression of the heart failure phenotype. Methods mCAT and wild type mice (n=10) were administered the non-selective beta-adrenergic agonist Isoprotenerol (Iso; 50mg/kg/day) through subcutaneous osmotic pumps for 3 weeks. Hearts were taken for biochemistry (western blotting, qPCR). Cardiomyocytes were isolated and loaded with Fluo-3 AM to study intracellular Ca2+ transients and fractional shortening using confocal line scan microscopy. All experiments were performed in accordance with the Stockholm ethical committee for animal research. Results and conclusions The WT mice displayed an increased heart/body weight ratio following chronic Iso administration. In contrast, mCAT mice displayed resistance to Iso-induced cardiac hypertrophy (p<0.05). Furthermore, chronic Iso exposure in WT mice induced increased ROS-dependent post-translational protein modifications, impaired cardiomyocyte Ca2+ handling and reduced contractility in isolated cardiomyocytes (p<0.05). Cardiomyocytes from mCAT mice did not display the deleterious effects of chronic Iso exposure on cardiomyocyte Ca2+ and contractility. Our study demonstrates that beta-adrenergic receptor stimulation-induced remodeling of the heart, which is similar to what is seen in heart failure, can be prevented by overexpressing catalase in the mitochondria. This indicates an important role of mitochondrial ROS in the link between adrenergic signaling and the development of cardiomyopathy and heart failure. Acknowledgement/Funding Hjärtlungfonden

scholarly journals Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
M. Neri ◽  
I. Riezzo ◽  
C. Pomara ◽  
S. Schiavone ◽  
E. Turillazzi
Keyword(s):  
Oxidative Stress ◽  
Current Literature ◽  
Cardiac Dysfunction ◽  
Nitrosative Stress ◽  
Myocardial Dysfunction ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Oxidative And Nitrosative Stress ◽  
Antioxidant Agents

Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients.Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis.Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

ROLE OF PREGNAN-X-RECEPTOR IN CELL RESISTANCE TO NITROSATIVE AND OXIDATIVE STRESS

2021 ◽  
Author(s):  
Yulia Abalenikhina ◽  
◽  
Elena A. Sudakova ◽  
Pelageya Erokhina ◽  
Aleksey Shchulkin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Viability ◽  
Nitrosative Stress ◽  
Pregnane X Receptor ◽  
Cell Resistance ◽  
Oxidative And Nitrosative Stress ◽  
High Concentrations ◽  
And Oxidative Stress

The article discusses the new role of pregnane X receptor (PXR) under conditions of oxidative and nitrosative stress. The results showed that the effect of hydrogen peroxide and S-nitrosoglu-tathione in high concentrations on Caco-2 cells leads to a decrease in cell viability, which is accompanied by an increase in the amount of PXR. These changes are offset by the addition of ketoconazole (inhibitor of PXR) to the medium.

Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver

2005 ◽  
Vol 156 (2-3) ◽  
pp. 101-111 ◽  
Author(s):  
Anil K Bansal ◽  
Manju Bansal ◽  
Giridhar Soni ◽  
Deepak Bhatnagar
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Rat Liver ◽  
Protective Role ◽  
Pre Treatment

scholarly journals Redox Homeostasis in Pancreatic Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Petr Ježek ◽  
Andrea Dlasková ◽  
Lydie Plecitá-Hlavatá
Keyword(s):  
Oxidative Stress ◽  
Insulin Release ◽  
Nitrosative Stress ◽  
Redox Homeostasis ◽  
Glucose Sensing ◽  
Redox Signaling ◽  
Regulatory Function ◽  
Peripheral Tissues ◽  
Information Signaling

We reviewed mechanisms that determine reactive oxygen species (redox) homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreaticβcells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion inβcell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreaticβcells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreaticβcells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreaticβcells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release.

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