scholarly journals Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase

2009 ◽  
Vol 587 (13) ◽  
pp. 3271-3285 ◽  
Author(s):  
Jessica R. Durrant ◽  
Douglas R. Seals ◽  
Melanie L. Connell ◽  
Molly J. Russell ◽  
Brooke R. Lawson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Nadph Oxidase ◽  
Endothelial Function ◽  
Direct Evidence ◽  
Wheel Running ◽  
Superoxide Dismutase Activity ◽  
Down Regulation ◽  
Old Mice ◽  
Voluntary Wheel

scholarly journals Voluntary wheel running abolishes vascular inflammation and restores endothelial function in old mice

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Melanie L Connell ◽  
Jessica R Durrant ◽  
Molly J Russell ◽  
Anthony J Donato ◽  
Douglas R Seals ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Wheel Running ◽  
Vascular Inflammation ◽  
Voluntary Wheel Running ◽  
Old Mice ◽  
Voluntary Wheel

Diazoxide Modulates Cardiac Hypertrophy by Targeting H2O2 Generation and Mitochondrial Superoxide Dismutase Activity

2020 ◽  
Vol 13 (1) ◽  
pp. 76-83
Author(s):  
Aline Maria Brito Lucas ◽  
Joana Varlla de Lacerda Alexandre ◽  
Maria Thalyne Silva Araújo ◽  
Cicera Edna Barbosa David ◽  
Yuana Ivia Ponte Viana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Cardiac Hypertrophy ◽  
Superoxide Dismutase Activity ◽  
Heart Weight ◽  
Pharmacological Intervention ◽  
Wall Thickening ◽  
H2o2 Production ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Superoxide Dismutase

Background: Cardiac hypertrophy involves marked wall thickening or chamber enlargement. If sustained, this condition will lead to dysfunctional mitochondria and oxidative stress. Mitochondria have ATP-sensitive K+ channels (mitoKATP) in the inner membrane that modulate the redox status of the cell. Objective: We investigated the in vivo effects of mitoKATP opening on oxidative stress in isoproterenol- induced cardiac hypertrophy. Methods: Cardiac hypertrophy was induced in Swiss mice treated intraperitoneally with isoproterenol (ISO - 30 mg/kg/day) for 8 days. From day 4, diazoxide (DZX - 5 mg/kg/day) was used in order to open mitoKATP (a clinically relevant therapy scheme) and 5-hydroxydecanoate (5HD - 5 mg/kg/day) or glibenclamide (GLI - 3 mg/kg/day) were used as mitoKATP blockers. Results: Isoproterenol-treated mice had elevated heart weight/tibia length ratios (HW/TL). Additionally, hypertrophic hearts had elevated levels of carbonylated proteins and Thiobarbituric Acid Reactive Substances (TBARS), markers of protein and lipid oxidation. In contrast, mitoKATP opening with DZX avoided ISO effects on gross hypertrophic markers (HW/TL), carbonylated proteins and TBARS, in a manner reversed by 5HD and GLI. Moreover, DZX improved mitochondrial superoxide dismutase activity. This effect was also blocked by 5HD and GLI. Additionally, ex vivo treatment of isoproterenol- induced hypertrophic cardiac tissue with DZX decreased H2O2 production in a manner sensitive to 5HD, indicating that this drug also acutely avoids oxidative stress. Conclusion: Our results suggest that diazoxide blocks oxidative stress and reverses cardiac hypertrophy. This pharmacological intervention could be a potential therapeutic strategy to prevent oxidative stress associated with cardiac hypertrophy.

scholarly journals Voluntary Aerobic Exercise Destiffens Arteries of Old Mice Via Inhibition of NADPH Oxidase‐ and Superoxide‐Dependent Oxidative Stress

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Jason Samuel Eng ◽  
Bryant Thanh Pham ◽  
Lawrence Cody Johnson ◽  
Rachel A Giosca‐Ryan ◽  
Douglas R Seals ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Aerobic Exercise ◽  
Old Mice

scholarly journals Aging increases vulnerability to stress-induced depression via upregulation of NADPH oxidase in mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jung-Eun Lee ◽  
Hye-Jin Kwon ◽  
Juli Choi ◽  
Ji-Seon Seo ◽  
Pyung-Lim Han
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Chronic Stress ◽  
Brain Aging ◽  
Aged Mice ◽  
Upstream Regulator ◽  
Underlying Mechanisms ◽  
Old Mice ◽  
And Oxidative Stress ◽  
Young Mice

AbstractBrain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippocampus, which mirrors the changes in young (2-month-old) mice subjected to chronic stress. Aged mice that lack p47phox, a key subunit of NADPH oxidase, do not show increased oxidative stress. Aged mice exhibit depression-like behavior following weak stress that does not produce depressive behavior in young mice. Aged mice have reduced expression of the epigenetic factor SUV39H1 and its upstream regulator p-AMPK, and increased expression of Ppp2ca in the hippocampus—changes that occur in young mice exposed to chronic stress. SUV39H1 mediates stress- and aging-induced sustained upregulation of p47phox and oxidative stress. These results suggest that aging increases susceptibility to stress by upregulating NADPH oxidase in the hippocampus.

scholarly journals P1143REDOX PROFILING IN MESOTHELIAL CELLS IN EXPERIMENTAL PERITONEAL DIALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Rebecca Herzog ◽  
Anja Wagner ◽  
Klaus Kratochwill
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Fluorescent Dyes ◽  
Mesothelial Cells ◽  
Superoxide Dismutase Activity ◽  
Cysteine Oxidation ◽  
Redox Stress ◽  
Redox Proteomics ◽  
Intracellular Ros ◽  
The Impact

Abstract Background and Aims PD-fluids lead to generation of reactive oxygen species (ROS) in the peritoneal cavity. The caused oxidative stress, defined as a cellular oxidant-antioxidant imbalance impairs not only peritoneal cell viability but also contributes to progression of local and systemic PD-related pathomechanisms. We aim to analyze the impact and specific targets of ROS during PD and the anti-oxidative mechanism of supplementation of PD-fluid with alanyl-glutamine (AlaGln) on a global proteome-wide level. Method To establish a redox-proteomics workflow for studying oxidative stress in peritoneal mesothelial cells we used a gold-standard model of redox-stress (H2O2) and PD-fluid induced stress. Levels of oxidative stress were first validated by increased intracellular ROS and superoxide dismutase activity with PD-fluid and H2O2 treatment and a reduction of these parameters by the addition of AlaGln. To detect alterations of the redox proteome, cysteine residues were either directly or indirectly labeled with fluorescent dyes (redox-2D-DiGE) or isobaric tags (iodo-TMT). Results: The gel-based approach allowed global visualization of the reduced and oxidized cysteines and revealed redox profiles of 540 protein spots. Compared to control, we found an increase in oxidized and decrease in reduced cysteines in all PD treatments. The development of a highly sensitive LC/MS-based redox proteomics workflow allowed identification of ∼950 proteins affected by redox-stress in mesothelial cells and confirmed the quantitative levels seen on cysteine oxidation. The addition of AlaGln reduced the overall redox status (intracellular ROS and superoxide dismutase activity) but further showed different proteins to be affected by redox modifications. Conclusion: Redox proteomics of peritoneal cells could represent a novel approach for the identification of mediators of PD-induced pathomechanisms, but also to evaluate effects of novel anti-oxidant therapeutical or pharmacological interventions.

Abstract 222: Exercise Training Prevents Rarefaction of Pial Collaterals, Promotes Cerebral Arterial Remodeling, and Lessens Severity of Stroke in Aging Brain

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wojciech J Rzechorzek ◽  
Brian K Buckley ◽  
Kunji Hua ◽  
Daniel Pomp ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Exercise Training ◽  
Wheel Running ◽  
Important Determinant ◽  
Fiber Type ◽  
Infarct Volume ◽  
Cerebral Arteries ◽  
Aging Brain ◽  
Old Mice

Variation in anatomic extent of the collateral circulation is an important determinant of variation in the severity of ischemic stroke and efficacy of revascularization therapies. Yet pial collateral number and lumen diameter decrease with age, at least in mice. It is not known if this can be mitigated. We tested whether exercise training can accomplish this and if it also affects diameter of the posterior communicating collalterals (PComs) and primary cerebral arteries (ICA, BA, MCA, ACA, PCA). We randomized 30 male and 30 female, 12 months-old (~40 human years, hy) C57BL/6J mice to either sedentary or voluntary wheel-running (daily distance run was measured). At 25 mos-age (~70 hy), permanent MCA occlusion was followed 24h later by vascular casting after maximal dilation and by determination of infarct volume. Controls for aging were 3 mos-old sedentary mice (~16 hy). Training effect was confirmed by muscle fiber-type switching, body weight and cardiac hypertrophy (all p<0.05). Exercise prevented age-associated loss of collateral number and diameter (p=0.049 and 0.005, n=13-14) and reduced infarct volume by 50%, ie, to that seen in 3 months-old mice (p=0.01, n=7). Unlike pial collaterals, PCom diameter and number (ie, present bilaterally, unilaterally or absent) were unaffected by exercise. Of further interest, diameter of the primary cerebral arteries increased with aging alone (119 ± 1 vs 134 ± 5 μm averaged combined diameter, p=0.02, n=10-14); this effect tended to increase further with exercise (143 ± 4 μm, p=0.07, n=13). Mechanistically, exercise increased vascular expression (assessed by immunohisto-chemistry) of total eNOS (p=0.03, n=5-6), phospho-eNOS (p=0.004, n=5) and a marker of anti-oxidative stress (SOD, p=0.008, n=5-6; but not HO-1, p=0.40, n=6). It did not alter a marker of aging (p16, p=0.42, n=5); analysis of additional targets is underway. In conclusion, exercise training prevented age-induced rarefaction of pial collaterals and reduced infarct volume. In addition and unexpectedly, aging also caused outward remodeling of the primary cerebral arteries, and exercise training tended to further augment this. These benefits of regular aerobic exercise were associated with increased eNOS bioavailability and reduced oxidative stress.

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