scholarly journals Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Daniëlle M. P. H. J. Boesten ◽  
Joyce M. J. de Vos-Houben ◽  
Leen Timmermans ◽  
Gertjan J. M. den Hartog ◽  
Aalt Bast ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Diseases ◽  
Human Fibroblasts ◽  
Methylation Status ◽  
Accelerated Aging ◽  
Chronic Inflammatory Disease ◽  
Telomere Shortening ◽  
Chronic Oxidative Stress ◽  
Linear Chromosomes ◽  
Parp 1

Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose) polymerase-1 (PARP-1) and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured under normal conditions and under conditions of chronic oxidative stress, induced bytert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.

scholarly journals Accelerated aging during chronic oxidative stress: a role for PARP‐1?

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Danielle M Boesten ◽  
Joyce M Houben ◽  
Leen Timmermans ◽  
Aalt Bast ◽  
Geja J Hageman
Keyword(s):  
Oxidative Stress ◽  
Accelerated Aging ◽  
Chronic Oxidative Stress ◽  
Parp 1

scholarly journals Chronic oxidative stress and telomere shortening

2007 ◽  
Vol 169 (2) ◽  
pp. 136 ◽  
Author(s):  
J.M.J. Houben ◽  
H.J.J. Moonen ◽  
F.J. van Schooten ◽  
G.J. Hageman
Keyword(s):  
Oxidative Stress ◽  
Telomere Shortening ◽  
Chronic Oxidative Stress

scholarly journals The green tea polyphenol EGCG is differentially associated with telomeric regulation in normal human fibroblasts versus cancer cells

2021 ◽  
Vol 11 (3) ◽  
pp. 73
Author(s):  
Angelika Pointner ◽  
Christine Mölzer ◽  
Ulrich Magnet ◽  
Katja Zappe ◽  
Berit Hippe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Green Tea ◽  
Epigenetic Regulation ◽  
Human Fibroblasts ◽  
Methylation Status ◽  
Epigallocatechin Gallate ◽  
Telomerase Activity ◽  
Tea Polyphenol ◽  
Green Tea Polyphenol

Introduction: Topical investigations have demonstrated that oxidative stress and inflammation play key roles in biological aging and determine incidence and course of age-related diseases. Lifestyle and environmental factors hugely impact epigenetic regulation and DNA stability with telomere attrition and epigenetic instability providing a potential record of the cumulative burden of endogenous and exogenous oxidative noxae. Certain physiologically active plant components exhibit antioxidative activities affecting epigenetic regulation of inflammation response and DNA repair.Methods: Against this background, the present study investigated green tea polyphenol epigallocatechin gallate (EGCG) in the context of telomere regulation in Caco-2 colorectal adenocarcinoma cells vs. ES-1 primary skin fibroblasts. Cell lines were treated with 20 and 200 µM EGCG for 36, 72 and 144 hours, respectively. Telomerase activity, relative telomere length as well as methylation status of hTERT and c-Myc from different culture conditions were assessed. Malondialdehyde (MDA) served as a surrogate marker of potential pro-oxidative effects of EGCG in a physiologically relevant tissue model.Results: EGCG incubation was associated with telomere shortening and decreased telomerase activity in Caco-2 cells, and relatively longer telomeres along with increased methylation of six 5'—C—phosphate—G—3' (CpG) sites in the promoter region of human Telomerase Reverse Transcriptase (hTERT) in fibroblasts. At low concentrations, EGCG significantly decreased oxidative damage to lipids in Caco-2 cells and attenuated H2O2 induced oxidation at higher concentrations.Conclusion: These results suggest differential EGCG-mediated telomeric modulation in cancer vs. primary cells and a specific antioxidant activity of EGCG against oxidative damage to lipids in abnormal cells.Keywords: Caco-2, epigallocatechin gallate, telomeres, hTERT, DNA methylation, telomerase, oxidative stress, malondialdehyde

scholarly journals Telomere Length in Transfusion Dependent Thalassemia Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1291-1291
Author(s):  
Nithita Nanthatanti ◽  
Adisak Tantiworawit ◽  
Nawapong Patpan ◽  
Thanawat Rattanathammethee ◽  
Sasinee Hantrakool ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Telomere Length ◽  
Restriction Fragment ◽  
Beta Thalassemia ◽  
Control Group ◽  
Ineffective Erythropoiesis ◽  
Chiang Mai ◽  
Telomere Shortening ◽  
Chronic Oxidative Stress

Abstract BACKGROUND Transfusion dependent thalassemia (TDT) patients is a group of thalassemia patients who require regular blood transfusion. Red blood cell transfusion and increased intestinal iron absorption leads to iron overload. The cellular damage associated with iron overload is mainly mediated by the state of oxidative stress and the effect of free oxygen radicals on various cell components. Telomeres are terminal protein-DNA complexes that stabilize chromosome and prevent DNA from double-stranded breaks. Chronic oxidative stress from iron overload and ineffective erythropoiesis in thalassemia may lead to shortening of telomere length. METHOD We conducted a cross-sectional study in TDT patients aged more than 18 years old who attended the adult hematology clinic at Maharaj Nakorn Chiang Mai hospital, Chiang Mai University, Thailand from 1 January 2016 to 30 April 2016. TDT was defined as thalassemia who requiring a red cell transfusion at least 3 times per year, included both beta-thalassemia and alpha-thalassemia patients. Telomere length was measured by real-time quantitative PCR and compared with matched healthy controls by age and sex. We used Pearson's correlation coefficient to test whether telomere length was associated with any factors. The threshold for statistical significance for all comparisons was chosen as P <0.05. RESULT Thirty TDT patients and 30 matched healthy control were included in this study. For TDT group, there were 19 female patients (63.3%). The median age was 29.2 (18-48) years. Baseline hemoglobin pre-transfusion 6.4 g/dL (5.3-7.4). Of these, there were 18 beta-thalassemia/Hb E disease (60%) who was the majority population. There were 11 beta-thalassemia major patients (36.4%) and 1 HbH with Constant spring patient (3.3%). The median telomeric terminal restriction fragment (TRF) length of TDT thalassemia group was 5.76 (4.94-7.13) kb. The median TRF length of control group was 6.79 (5.52-9.02) kb. TDT patients had significant shorter TRF length compared to control group (age and sex match), (p<0.0001). Telomere shortening in TDT thalassemia is aging-dependent process. The Pearson's coefficient showed the negative correlation between TRF length and age (Pearson's coefficient = 0.176), (p=0.021). There was no correlation of telomere length with other factors such as sex, hemoglobin level, transfusion requirement. CONCLUSION TDT patients had shorter telomere length compared to control group. Telomere shortening in TDT thalassemia is aging-dependent process. Chronic oxidative stress from iron overload and ineffective erythropoiesis in thalassemia may play the significant role in this accelerated telomere shortening process. Table The median telomeric terminal restriction fragment length of TDT patients compared with control group Table. The median telomeric terminal restriction fragment length of TDT patients compared with control group Disclosures No relevant conflicts of interest to declare.

scholarly journals Pulmonary Hypertension Is a Probable NO/ONOO− Cycle Disease: A Review

2013 ◽  
Vol 2013 ◽  
pp. 1-27 ◽  
Author(s):  
Martin L. Pall
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Pulmonary Arteries ◽  
Chronic Inflammatory Disease ◽  
Vicious Cycle ◽  
Chronic Inflammatory Diseases ◽  
Local Mechanism ◽  
Pulmonary Arterial ◽  
Symptoms And Signs

The NO/ONOO− cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic inflammatory diseases. This paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. The cycle involves 12 elements, including superoxide, peroxynitrite (ONOO−), nitric oxide (NO), oxidative stress, NF-κB, inflammatory cytokines, iNOS, mitochondrial dysfunction, intracellular calcium, tetrahydrobiopterin depletion, NMDA activity, and TRP receptor activity. 10 of the 12 are elevated in PAH (NMDA?, NO?) and 11 have documented causal roles in PAH. Each stressor that initiates cases of PAH acts to raise cycle elements, and may, therefore, initiate the cycle in this way. PAH involves a primarily local mechanism as required by the cycle and the symptoms and signs of PAH are generated by elements of the cycle. Endothelin-1, which acts as a causal factor in PAH, acts as part of the cycle; its synthesis is stimulated by cycle elements, and it, in turn, increases each element of the cycle. This extraordinary fit to the principles of the NO/ONOO− cycle allows one to conclude that PAH is a NO/ONOO− cycle disease, and this fit supports the cycle as a major paradigm of chronic inflammatory disease.

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

scholarly journals Neurotherapeutic Effect of Inula britannica var. Chinensis against H2O2-Induced Oxidative Stress and Mitochondrial Dysfunction in Cortical Neurons

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 375
Author(s):  
Jin Young Hong ◽  
Hyunseong Kim ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
Seung Ho Baek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cortical Neurons ◽  
Inflammatory Diseases ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects ◽  
Neuronal Viability ◽  
Inula Britannica ◽  
Oxidative Effects

Inula britannica var. chinensis (IBC) has been used as a traditional medicinal herb to treat inflammatory diseases. Although its anti-inflammatory and anti-oxidative effects have been reported, whether IBC exerts neuroprotective effects and the related mechanisms in cortical neurons remain unknown. In this study, we investigated the effects of different concentrations of IBC extract (5, 10, and 20 µg/mL) on cortical neurons using a hydrogen peroxide (H2O2)-induced injury model. Our results demonstrate that IBC can effectively enhance neuronal viability under in vitro-modeled reaction oxygen species (ROS)-generating conditions by inhibiting mitochondrial ROS production and increasing adenosine triphosphate level in H2O2-treated neurons. Additionally, we confirmed that neuronal death was attenuated by improving the mitochondrial membrane potential status and regulating the expression of cytochrome c, a protein related to cell death. Furthermore, IBC increased the expression of brain-derived neurotrophic factor and nerve growth factor. Furthermore, IBC inhibited the loss and induced the production of synaptophysin, a major synaptic vesicle protein. This study is the first to demonstrate that IBC exerts its neuroprotective effect by reducing mitochondria-associated oxidative stress and improving mitochondrial dysfunction.

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