Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

Spaceflight causes cardiovascular changes due to microgravity-induced redistribution of body fluids and musculoskeletal unloading. Cardiac deconditioning and atrophy on Earth are associated with altered Trp53 and oxidative stress-related pathways, but the effects of spaceflight on cardiac changes at the molecular level are less understood. We tested the hypothesis that spaceflight alters the expression of key genes related to stress response pathways, which may contribute to cardiovascular deconditioning during extended spaceflight. Mice were exposed to spaceflight for 15 days or maintained on Earth (ground control). Ventricle tissue was harvested starting ~3 h post-landing. We measured expression of select genes implicated in oxidative stress pathways and Trp53 signaling by quantitative PCR. Cardiac expression levels of 37 of 168 genes tested were altered after spaceflight. Spaceflight downregulated transcription factor, Nfe2l2 (Nrf2), upregulated Nox1 and downregulated Ptgs2, suggesting a persistent increase in oxidative stress-related target genes. Spaceflight also substantially upregulated Cdkn1a (p21) and cell cycle/apoptosis-related gene Myc, and downregulated the inflammatory response gene Tnf. There were no changes in apoptosis-related genes such as Trp53. Spaceflight altered the expression of genes regulating redox balance, cell cycle and senescence in cardiac tissue of mice. Thus, spaceflight may contribute to cardiac dysfunction due to oxidative stress.

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SJSZ Glycoprotein (38 kDa) Inhibits Cell Cycle and Oxidative Stress in N-Methyl-N`- nitro-N-nitrosoguanidine-induced ICR Mice

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520611313040013 ◽

2013 ◽

Vol 13 (4) ◽

pp. 647-653 ◽

Cited By ~ 1

Author(s):

Jin Lee ◽

Kye-Taek Lim

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Icr Mice ◽

And Oxidative Stress

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Hydrogen peroxide and quercetin induced changes on cell viability, apoptosis and oxidative stress in HepG2 cells

Current Nutraceuticals ◽

10.2174/2665978601999200807160528 ◽

2020 ◽

Vol 01 ◽

Author(s):

Ayşe Mine Yılmaz ◽

Gökhan Biçim ◽

Kübra Toprak ◽

Betül Karademir Yılmaz ◽

Irina Milisav ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Hydrogen Peroxide ◽

Cell Viability ◽

Hepg2 Cells ◽

Proteasome Activity ◽

Cell Cycle Phases ◽

Induced Changes ◽

And Oxidative Stress ◽

Quercetin Treatment

Background: Different cellular responses influence the progress of cancer. In this study, we have investigated the effect of hydrogen peroxide and quercetin induced changes on cell viability, apoptosis and oxidative stress in human hepatocellular carcinoma (HepG2) cells. Methods: The effects of hydrogen peroxide and quercetin on cell viability, cell cycle phases and oxidative stress related cellular changes were investigated. Cell viability was assessed by WST-1 assay. Apoptosis rate, cell cycle phase changes and oxidative stress were measured by flow cytometry. Protein expressions of p21, p27, p53, NF-Kβ-p50 and proteasome activity were determined by Western blot and fluorometry, respectively. Results: Hydrogen peroxide and quercetin treatment resulted in decreased cell viability and increased apoptosis in HepG2 cells. Proteasome activity was increased by hydrogen peroxide but decreased by quercetin treatment. Conclusion: Both agents resulted in decreased p53 protein expression and increased cell death by different mechanisms regarding proteostasis and cell cycle phases.

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Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet

Antioxidants ◽

10.3390/antiox10050769 ◽

2021 ◽

Vol 10 (5) ◽

pp. 769

Author(s):

Patoomporn Prasatthong ◽

Sariya Meephat ◽

Siwayu Rattanakanokchai ◽

Juthamas Khamseekaew ◽

Sarawoot Bunbupha ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Tissue ◽

Sprague Dawley ◽

High Fat ◽

Impaired Liver Function ◽

Impaired Liver ◽

Cardiometabolic Disorders ◽

Cox 2 ◽

Factor Α ◽

And Oxidative Stress

Galangin is a natural flavonoid. In this study, we evaluated whether galangin could alleviate signs of metabolic syndrome (MS) and cardiac abnormalities in rats receiving a high-fat (HF) diet. Male Sprague–Dawley rats were given an HF diet plus 15% fructose for four months, and they were fed with galangin (25 or 50 mg/kg), metformin (100 mg/kg), or a vehicle for the last four weeks. The MS rats exhibited signs of MS, hypertrophy of adipocytes, impaired liver function, and cardiac dysfunction and remodeling. These abnormalities were alleviated by galangin (p < 0.05). Interleukin-6 and tumor necrosis factor-α concentrations and expression were high in the plasma and cardiac tissue in the MS rats, and these markers were suppressed by galangin (p < 0.05). These treatments also alleviated the low levels of adiponectin and oxidative stress induced by an HF diet in rats. The downregulation of adiponectin receptor 1 (AdipoR1) and cyclooxygenase-2 (COX-2) and the upregulation of nuclear factor kappa B (NF-κB) expression were recovered in the galangin-treated groups. Metformin produced similar effects to galangin. In conclusion, galangin reduced cardiometabolic disorders in MS rats. These effects might be linked to the suppression of inflammation and oxidative stress and the restoration of AdipoR1, COX-2, and NF-κB expression.

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Abstract 305: Nebivolol Confers Mitochondria-Targeted Cardioprotection in Isoproterenol-Induced Acute Stressor State

Circulation Research ◽

10.1161/res.111.suppl_1.a305 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Sumeet S Vaikunth ◽

Karl T Weber ◽

Syamal K Bhattacharya

Keyword(s):

Oxidative Stress ◽

Cardiac Tissue ◽

Mitochondrial Permeability Transition ◽

Therapeutic Potential ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Antioxidant Defenses ◽

Sprague Dawley ◽

Acute Stressor ◽

And Oxidative Stress

Introduction: Isoproterenol-induced acute stressor state simulates injury from burns or trauma, and results in Ca 2+ overloading and oxidative stress in diverse tissues, including cardiac myocytes and their subsarcolemmal mitochondria (SSM), overwhelming endogenous Zn 2+ -based antioxidant defenses. We hypothesized that pretreatment with nebivolol (Nebi), having dual beta-1 antagonistic and novel beta-3 receptor agonistic properties, would prevent Ca 2+ overloading and oxidative stress and upregulate Zn 2+ -based antioxidant defenses, thus enhancing its overall cardioprotective potential in acute stressor state. Methods: Eight-week-old male Sprague-Dawley rats received a single subcutaneous dose of isoproterenol (1 mg/kg) and compared to those treated with Nebi (10 mg/kg by gavage) for 10 days prior to isoproterenol. SSM were harvested from cardiac tissue at sacrifice. Total Ca 2+ , Zn 2+ and 8-isoprostane levels in tissue, and mitochondrial permeability transition pore (mPTP) opening, free [Ca 2+ ] m and H 2 O 2 production in SSM were monitored. Untreated, age-/sex-matched rats served as controls; each group had six rats and data shown as mean±SEM. Results: Compared to controls, isoproterenol rats revealed: (1) Significantly (*p<0.05) increased cardiac tissue Ca 2+ (8.2±0.8 vs. 13.7±1.0*, nEq/mg fat-free dry tissue (FFDT)), which was abrogated ( # p<0.05) by Nebi (8.9±0.4 # ); (2) Reduced cardiac Zn 2+ (82.8±2.4 vs. 78.5±1.0*, ng/mg FFDT), but restored by Nebi (82.4±0.6 # ); (3) Two-fold rise in cardiac 8-isoprostane (111.4±13.7 vs. 232.1±17.2*, pmoles/mg protein), and negated by Nebi (122.3+14.5 # ); (4) Greater opening propensity for mPTP that diminished by Nebi; (5) Elevated [Ca 2+ ] m (88.8±2.5 vs. 161.5±1.0*, nM), but normalized by Nebi (93.3±2.7 # ); and (6) Increased H 2 O 2 production by SSM (97.4±5.3 vs. 142.8±7.0*, pmoles/mg protein/min), and nullified by Nebi (106.8±9.0 # ). Conclusions : Cardioprotection conferred by Nebi, a unique beta-blocker, prevented Ca 2+ overloading and oxidative stress in cardiac tissue and SSM, while simultaneously augmenting antioxidant capacity and promoting mPTP stability. Therapeutic potential of Nebi in patients with acute stressor states remains a provocative possibility that deserves to be explored.

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Hypoxia-induced myocardial regeneration

Journal of Applied Physiology ◽

10.1152/japplphysiol.00328.2017 ◽

2017 ◽

Vol 123 (6) ◽

pp. 1676-1681 ◽

Cited By ~ 15

Author(s):

Wataru Kimura ◽

Yuji Nakada ◽

Hesham A. Sadek

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Systolic Heart Failure ◽

Cardiac Regeneration ◽

Oxygen Metabolism ◽

Functional Improvement ◽

Cardiomyocyte Proliferation ◽

Mammalian Heart ◽

Cell Cycle Reentry ◽

And Oxidative Stress

The underlying cause of systolic heart failure is the inability of the adult mammalian heart to regenerate damaged myocardium. In contrast, some vertebrate species and immature mammals are capable of full cardiac regeneration following multiple types of injury through cardiomyocyte proliferation. Little is known about what distinguishes proliferative cardiomyocytes from terminally differentiated, nonproliferative cardiomyocytes. Recently, several reports have suggested that oxygen metabolism and oxidative stress play a pivotal role in regulating the proliferative capacity of mammalian cardiomyocytes. Moreover, reducing oxygen metabolism in the adult mammalian heart can induce cardiomyocyte cell cycle reentry through blunting oxidative damage, which is sufficient for functional improvement following myocardial infarction. Here we concisely summarize recent findings that highlight the role of oxygen metabolism and oxidative stress in cardiomyocyte cell cycle regulation, and discuss future therapeutic approaches targeting oxidative metabolism to induce cardiac regeneration.

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Effects of stanozolol on apoptosis mechanisms and oxidative stress in rat cardiac tissue

Steroids ◽

10.1016/j.steroids.2018.02.004 ◽

2018 ◽

Vol 134 ◽

pp. 96-100 ◽

Cited By ~ 3

Author(s):

Mehtap Kara ◽

Eren Ozcagli ◽

Tuğba Kotil ◽

Buket Alpertunga

Keyword(s):

Oxidative Stress ◽

Cardiac Tissue ◽

And Oxidative Stress

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The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats

Renal Failure ◽

10.3109/0886022x.2014.991996 ◽

2015 ◽

Vol 37 (2) ◽

pp. 192-197 ◽

Cited By ~ 8

Author(s):

Aydın Güçlü ◽

Nilüfer Yonguç ◽

Yavuz Dodurga ◽

Gülşah Gündoğdu ◽

Zuhal Güçlü ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Grape Seed ◽

Diabetic Rats ◽

Related Gene ◽

And Oxidative Stress ◽

Apoptosis Related Gene

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Methodologies to Assess the Bioactivity of an Herbal Extract on Immunity, Health, Welfare and Production Performance in the Chicken: The Case of Melissa officinalis L. Extract

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.759456 ◽

2021 ◽

Vol 8 ◽

Author(s):

Angélique Travel ◽

Angélique Petit ◽

Perrine Barat ◽

Anne Collin ◽

Camille Bourrier-Clairat ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Cells ◽

Ex Vivo ◽

Redox Balance ◽

Herbal Extracts ◽

Melissa Officinalis ◽

Starting Conditions ◽

Anti Inflammatory ◽

And Oxidative Stress

The potential of herbal extracts containing bioactive compounds to strengthen immunity could contribute to reducing antimicrobial use in poultry. This study aimed at developing a reliable and robust methodological pipeline to assess the ability of herbal extracts to strengthen chicken innate defenses, especially concerning inflammation and oxidative stress. This methodology was applied to Melissa officinalis L. (MEL) extract, recognized for its biological activities including antioxidant and anti-inflammatory properties. Different methods were used to (1). guarantee the quality of MEL extract and its capacity to stimulate the innate immune system; (2). evaluate the relevance of an ex vivo model to mimic inflammatory and oxidative stress challenges to replace LPS injection in chickens; (3). analyse the effects of feed supplemented with MEL extract on inflammation and oxidative stress induced ex vivo; (4). assess the effects of MEL extract on the redox balance, health, welfare and performance in broilers exposed to suboptimal starting conditions through a large-scale approach. The quality of MEL extract preparations, through phytochemical quantification of rosmarinic acid (RA), revealed varying concentrations of RA in the different MEL extracts. RA concentrations remained stable for at least 9 months and in feed three months after incorporating MEL extract. When incubated with chicken cell lines MEL extract showed potential metabolic activation and ability to stimulate immune functions but induced cytotoxicity at high concentrations. The original ex vivo model of inflammation developed on chicken blood cells enabled inflammation and oxidative stress biomarkers to be expressed and revealed antioxidative and anti-inflammatory properties of blood cells from chickens fed MEL extract. The experimental model of chicken suboptimal starting conditions validated beneficial effects of MEL extract on the redox balance and also evidenced improved performance during the growth phase, a tendency for fewer muscle defects but a higher severity of pododermatitis lesions without affecting other welfare indicators. This study grouped methods and tools that could be combined according to the plant extract, the needs of professionals working in poultry production systems and staff responsible for animal health, welfare and feeding.

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