scholarly journals Oxygen Radicals Elicit Paralysis and Collapse of Spinal Cord Neuron Growth Cones upon Exposure to Proinflammatory Cytokines

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Thomas B. Kuhn
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Nadph Oxidase ◽  
Proinflammatory Cytokines ◽  
Growth Cone ◽  
Growth Cones ◽  
Neuronal Morphology ◽  
Dependent Manner ◽  
Spinal Cord Neuron ◽  
Cord Neuron

A persistent inflammatory and oxidative stress is a hallmark of most chronic CNS pathologies (Alzheimer’s (ALS)) as well as the aging CNS orchestrated by the proinflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β). Loss of the integrity and plasticity of neuronal morphology and connectivity comprises an early step in neuronal degeneration and ultimate decline of cognitive function. We examinedin vitrowhether TNFαor IL-1βimpaired morphology and motility of growth cones in spinal cord neuron cultures. TNFαand IL-1βparalyzed growth cone motility and induced growth cone collapse in a dose-dependent manner reflected by complete attenuation of neurite outgrowth. Scavenging reactive oxygen species (ROS) or inhibiting NADPH oxidase activity rescued loss of neuronal motility and morphology. TNFαand IL-1βprovoked rapid, NOX-mediated generation of ROS in advancing growth cones, which preceded paralysis of motility and collapse of morphology. Increases in ROS intermediates were accompanied by an aberrant, nonproductive reorganization of actin filaments. These findings suggest that NADPH oxidase serves as a pivotal source of oxidative stress in neurons and together with disruption of actin filament reorganization contributes to the progressive degeneration of neuronal morphology in the diseased or aging CNS.

Abstract 107: Apocynin Attenuates Isoproterenol-induced Myocardial Injury: Implications For Targeting Nadph Oxidase In Myocardial Fibrogenesis

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Yu Chen ◽  
Jingang Cui ◽  
Qinbo Yang ◽  
Chenglin Jia ◽  
Minqi Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Myocardial Fibrosis ◽  
Myocardial Injury ◽  
Oxidase Inhibitor ◽  
Ros Generation ◽  
Dependent Manner ◽  
Expression Of Genes ◽  
Therapeutic Development ◽  
Myocardial Injuries

Myocardial fibrosis results from cardiac injuries caused by various pathophysiological mechanisms including myocardial infarction, leading to destruction of myocardial architecture and progressive cardiac dysfunction. Oxidative stress is likely involved in myocardial ischemic injury and the subsequent tissue remodeling mediated by myocardial fibrogenesis. Our current study aimed to evaluate the implication of NADPH oxidase in overproduction of reactive oxygen species and its contribution to the pathogenesis of myocardial fibrogenesis after ischemic injuries. The effects of Apocynin, a selective NADPH oxidase inhibitor, were evaluated in the mouse model of isoproterenol-induced myocardial injury by histopathological approaches and whole-genome gene expression profiling. The results demonstrated that Apocynin was able to inhibit the development of ISO-induced myocardial necrotic lesions and fibrogenesis in a dose-dependent manner. Moreover, the preventive effects of Apocynin on myocardial injuries were associated with suppressed expression of genes implicated in inflammation responses and extracellular matrix, which were remarkably upregulated by isoproterenol administration. In summary, o ur study provides proof-of-concept for the involvement of NADPH oxidase-mediated ROS generation in myocardial ischemic injuries and fibrogenesis, which will benefit the mechanism-based therapeutic development targeting NADPH oxidase and oxidative stress in treating myocardial fibrosis and related disorders.

scholarly journals Effect of Anthocyanin-Rich Extract of Sour Cherry for Hyperglycemia-Induced Inflammatory Response and Impaired Endothelium-Dependent Vasodilation

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3373
Author(s):  
Arnold Markovics ◽  
Attila Biró ◽  
Andrea Kun-Nemes ◽  
Mónika Éva Fazekas ◽  
Anna Anita Rácz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Sour Cherry ◽  
The Elderly ◽  
Human Umbilical Cord ◽  
Dependent Manner

Diabetes mellitus (DM)-related morbidity and mortality are steadily rising worldwide, affecting about half a billion people worldwide. A significant proportion of diabetic cases are in the elderly, which is concerning given the increasing aging population. Proper nutrition is an important component in the effective management of diabetes in the elderly. A plethora of active substances of plant origin exhibit potency to target the pathogenesis of diabetes mellitus. The nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. In this study, the effect of Hungarian sour cherry, which is rich in anthocyanins, on hyperglycemia-induced endothelial dysfunction was tested using human umbilical cord vein endothelial cells (HUVECs). HUVECs were maintained under both normoglycemic (5 mM) and hyperglycemic (30 mM) conditions with or without two concentrations (1.50 ng/µL) of anthocyanin-rich sour cherry extract. Hyperglycemia-induced oxidative stress and inflammatory response and damaged vasorelaxation processes were investigated by evaluating the level of reactive oxygen species (ROS) and gene expression of four proinflammatory cytokines, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1α (IL-1α), as well as the gene expression of nitric oxide synthase (NOS) endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1). It was found that hyperglycemia-induced oxidative stress was significantly suppressed by anthocyanin-rich sour cherry extract in a concentration-dependent manner. The gene expression of the tested proinflammatory cytokines increased under hyperglycemic conditions but was significantly reduced by both 1 and 50 ng/µL anthocyanin-rich sour cherry extract. Further, although increased ET-1 and ECE-1 expression due to hyperglycemia was reduced by anthocyanin-rich sour cherry extract, NOS expression was increased by the extract. Collectively, these data suggest that anthocyanin-rich sour cherry extract could alleviate hyperglycemia-induced endothelial dysfunction due to its antioxidant, anti-inflammatory, and vasorelaxant effects.

scholarly journals pH-responsive delivery of H2 through ammonia borane-loaded mesoporous silica nanoparticles improves recovery after spinal cord injury by moderating oxidative stress and regulating microglial polarization

2021 ◽  
Author(s):  
Yi Liu ◽  
Yeying Wang ◽  
Bing Xiao ◽  
Guoke Tang ◽  
Jiangming Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Ammonia Borane ◽  
Neural Regeneration ◽  
Dependent Manner ◽  
Cord Injury

Abstract Imbalance of oxidative and inflammatory regulation is the main contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury (SCI). As an emerging biosafe strategy for protecting against oxidative and inflammatory damage, hydrogen (H2) therapy is a promising approach for improving the microenvironment to allow neural regeneration. However, achieving release of H2 at sufficient concentrations specifically into the injured area is critical for the therapeutic effect of H2. Thus, we assembled SiO2@mSiO2 mesoporous silica nanoparticles and loaded them with ammonia borane (AB), which has abundant capacity and allows controllable release of H2 in an acid-dependent manner. The release of H2 from AB/SiO2@mSiO2 was satisfactory at pH 6.6, which is approximately equal to the microenvironmental acidity after SCI. After AB/SiO2@mSiO2 were intrathecally administered to rat models of SCI, continuous release of H2 from these nanoparticles synergistically enhanced neurofunctional recovery, reduced fibrotic scar formation and promoted neural regeneration by suppressing oxidative stress reaction. Furthermore, in the subacute phase of SCI, microglia were markedly polarized toward the M2 phenotype by H2 via inhibition of TLR9 expression in astrocytes. In conclusion, H2 delivery through AB/SiO2@mSiO2 has the potential to efficiently treat SCI through comprehensive modulation of the oxidative and inflammatory imbalance in the microenvironment.

Curcumin ameliorated diabetic neuropathy partially by inhibition of NADPH oxidase mediating oxidative stress in the spinal cord

2014 ◽  
Vol 560 ◽  
pp. 81-85 ◽  
Author(s):  
Wei-Cheng Zhao ◽  
Bin Zhang ◽  
Mei-Juan Liao ◽  
Wen-Xuan Zhang ◽  
Wan-You He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Nadph Oxidase ◽  
Diabetic Neuropathy

Abstract 123: Age-Related Endothelial Senescence is Driven by Thrombospondin-1-Activated NADPH Oxidase Nox1

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Daniel N Meijles ◽  
Imad Al Ghouleh ◽  
Sanghamitra Sahoo ◽  
Jefferson H Amaral ◽  
Heather Knupp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Vascular Diseases ◽  
Dependent Manner ◽  
Wild Type ◽  
Molecular Control ◽  
Redox Biology ◽  
Age Related ◽  
P53 Activation

Organismal aging represents an independent risk factor underlying many vascular diseases, including systemic and pulmonary hypertension, and atherosclerosis. While the mechanisms driving aging are largely elusive, a steady persistent increase in tissue oxidative stress has been associated with senescence. Previously we showed TSP1 elicits NADPH oxidase (Nox)-dependent vascular smooth muscle cell oxidative stress. However mechanisms by which TSP1 affects endothelial redox biology are unknown. Here, we tested the hypothesis that TSP1 induces endothelial oxidative stress-linked senescence in aging. Using rapid autopsy disease-free human pulmonary (PA) artery, we identified a significant positive correlation between age, protein levels of TSP1, Nox1 and the cell-cycle repressor p21cip (p<0.05). Age also positively associated with increased Amplex Red-detected PA hydrogen peroxide levels (p<0.05). Moreover, treatment of human PA endothelial cells (HPAEC) with TSP1 (2.2nM; 24h) increased expression (~1.9 fold; p<0.05) and activation of Nox1 (~1.7 fold; p<0.05) compared to control, as assessed by Western blot and SOD-inhibitable cytochrome c reduction. Western blotting and immunofluorescence showed a TSP1-mediated increase in p53 activation, indicative of the DNA damage response. Moreover, TSP1 significantly increased HPAEC senescence in a p53/p21cip/Rb-dependent manner, as assessed by immunofluorescent detection of subcellular localization and senescence-associated β-galactosidase staining. To explore this pathway in vivo, middle-aged (8-10 month) wild-type and TSP1-null mice were utilized. In the TSP1-null, reduced lung senescence, oxidative stress, Nox1 levels and p21cip expression were observed compared to wild-type supporting findings in human samples and cell experiments. Finally, prophylactic treatment with specific Nox1 inhibitor NoxA1ds (10μM) attenuated TSP1-induced HPAEC ROS, p53 activation, p21cip expression and senescence. Taken together, our results provide molecular insight into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence, with implications for molecular control of the aging process.

An inhibitory spinal cord neuron

JAMA ◽  
1980 ◽  
Vol 244 (22) ◽  
pp. 2555-2555
Author(s):  
E. A. Neale
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Neuron ◽  
Cord Neuron

scholarly journals Angiotensin II type 1 receptor blocker attenuates the activation of ERK and NADPH oxidase by mechanical strain in mesangial cells in the absence of angiotensin II

2009 ◽  
Vol 296 (5) ◽  
pp. F1052-F1060 ◽  
Author(s):  
Junichi Yatabe ◽  
Hironobu Sanada ◽  
Midori Sasaki Yatabe ◽  
Shigeatsu Hashimoto ◽  
Minoru Yoneda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mesangial Cells ◽  
Mechanical Strain ◽  
Dependent Manner ◽  
Ang Ii ◽  
Erk Phosphorylation ◽  
Extracellular Signal

It has been reported that mechanical strain activates extracellular signal-regulated protein kinases (ERK) without the involvement of angiotensin II (Ang II) in cardiomyocytes. We examined the effects of mechanical strain on ERK phosphorylation levels in the absence of Ang II using rat mesangial cells. The ratio of phosphorylated ERK (p-ERK) to total ERK expression was increased by cyclic mechanical strain in a time- and elongation strength-dependent manner. With olmesartan [Ang II type 1 receptor (AT1R) antagonist] pretreatment, p-ERK plateau levels decreased in a dose-dependent manner (EC50 = 1.3 × 10−8 M, maximal inhibition 50.6 ± 11.0% at 10−5 M); a similar effect was observed with RNA interference against Ang II type 1A receptor (AT1AR) and Tempol, a superoxide dismutase mimetic. In addition to the inhibition of p-ERK levels, olmesartan blocked the increase in cell surface and phosphorylated p47phox induced by mechanical strain and also lowered the mRNA expression levels of NADPH oxidase subunits. These results demonstrate that mechanical strain stimulates AT1R to phosphorylate ERK in mesangial cells in the absence of Ang II. This mechanotransduction mechanism is involved in the oxidative stress caused by NADPH oxidase and is blocked by olmesartan. The inverse agonistic activity of this AT1R blocker may be useful for the prevention of mesangial proliferation and renal damage caused by mechanical strain/oxidative stress regardless of circulating or tissue Ang II levels.

scholarly journals Nrf2 Activation Attenuates Chronic Constriction Injury-induced Neuropathic Pain via Induction of PGC-1α-mediated Mitochondrial Biogenesis in the Spinal Cord

2021 ◽  
Author(s):  
Jia Sun ◽  
Jia-Yan Li ◽  
Long-Qing Zhang ◽  
Dan-Yang Li ◽  
Jia-Yi Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Chronic Constriction Injury ◽  
Clinical Investigation ◽  
Thermal Hyperalgesia ◽  
Related Factor ◽  
Dependent Manner

Abstract BackgroundNeuropathic pain is a debilitating disease with few effective treatments. Emerging evidence indicates the involvement of mitochondrial dysfunction and oxidative stress in neuropathic pain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a potent regulator of antioxidant response system. In this study, we investigated whether RTA-408 (a novel synthetic triterpenoid under clinical investigation) could activate Nrf2 and promote mitochondrial biogenesis (MB) to reverse neuropathic pain and the underlying mechanisms.MethodsNeuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Pain behaviors were measured via the von-Frey test and Hargreaves plantar test. The L4-6 spinal cord was collected to examine the activation of Nrf2 and MB.ResultsRTA-408 treatment significantly reversed mechanical allodynia and thermal hyperalgesia in CCI mice in a dose-dependent manner. Furthermore, RTA-408 increased the activity of Nrf2 and significantly restored MB that was impaired in CCI mice in an Nrf2 dependent manner. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) is the key regulator of MB. We found that PGC-1α activator also exhibited a potent analgesic effect in CCI mice. Moreover, the antinociceptive effect of RTA-408 was reversed by the pre-injection of PGC-1α inhibitor.ConclusionsNrf2 activation attenuates chronic constriction injury-induced neuropathic pain via induction of PGC-1α-mediated mitochondrial biogenesis in the spinal cord. Our results indicate that Nrf2 may be a potential therapeutic strategy to ameliorate neuropathic pain and many other disorders with oxidative stress and mitochondrial dysfunction.

Abstract 200: CD40 Signaling Mediates Postischemic Inflammation, Oxidative Stress, And Tissue Injury Following Focal Cerebral Ischemia

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Rong Jin ◽  
Zifang Song ◽  
Shiyong Yu ◽  
Daniel J Daunis ◽  
Brittany S Hopkins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Tissue Damage ◽  
Tissue Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Wild Type ◽  
Cox 2

Rationale: Although CD40/CD40 ligand (CD40L) signaling has been implicated in clinical and experimental ischemic strokes, the underlying mechanisms are largely unclear. Objective: We investigated how CD40 participates in the cellular and molecular events underlying the postischemic inflammation and oxidative stress that may contribute to the tissue damage during cerebral ischemia. Methods and Results: Wild-type (WT, n=164) and CD40 knockout mice (n=132) were subjected to middle cerebral artery occlusion (MCAO, 60 minutes) followed by reperfusion. We found that ischemia/reperfusion induced CD40 expression in the brain in a time-dependent manner, primarily localized to the microvascular endothelial cells in the early phase (6h) and then to the activated microglia in the later time (24h). The adhesion and infiltration of neutrophils as well as the activation and expansion of microglia induced by ischemia/reperfusion were inhibited in CD40-/- mice, which were time-dependently correlated with suppressing nuclear factor-kB activation and proinflammatory cytokines (IL-1β, TNFα) and adhesion molecules (E- and P-selectin, ICAM-1,MCP-1). Infarct volumes and mortality were reduced in CD40-/- mice at 72h after ischemia/reperfusion. Treatment with an inhibitor of either NADPH oxidase or COX-2, the known enzymes that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD40-/- mice. In contrast, treatment with an inhibitor of inducible nitric oxide synthase (iNOS) further reduced tissue injury in CD40-/- mice. Consistently, ischemia/reperfusion-induced upregulation of NADPH oxidase (Nox2, and Nox4) and COX-2, but not iNOS, were attenuated in CD40-/- mice. Conclusions: The findings unveil an essential role for CD40 in the regulation of early molecular and cellular events leading to postischemic inflammation. Inhibition of CD40 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

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