Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation

1999 ◽  
Vol 87 (5) ◽  
pp. 1734-1740 ◽  
Author(s):  
John G. Wood ◽  
Jennifer S. Johnson ◽  
Leone F. Mattioli ◽  
Norberto C. Gonzalez
Keyword(s):  
Functional Relationship ◽  
Ros Generation ◽  
Oxygen Species ◽  
Leukocyte Adherence ◽  
Systemic Hypoxia ◽  
Signal Changes ◽  
Adhesive Interactions ◽  
Reactive Oxidant ◽  
Mesenteric Microcirculation

We recently demonstrated that systemic hypoxia during reduced inspired [Formula: see text] produces a rapid increase in leukocyte adherence to rat mesenteric venules. Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could involve increased reactive oxygen species (ROS) generation resulting in inactivation of NO. The overall goal of the present study was to examine the role of ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2) determine how the ROS signal changes when [Formula: see text] levels return to normal after a period of systemic hypoxia, 3) assess the effect of antioxidants on ROS generation during hypoxia, and 4) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major findings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the increase in leukocyte-endothelial adhesive interactions observed in hypoxia.

Leukotriene B4 promotes reactive oxidant generation and leukocyte adherence during acute hypoxia

2001 ◽  
Vol 91 (3) ◽  
pp. 1160-1167 ◽  
Author(s):  
Dawn R. S. Steiner ◽  
Norberto C. Gonzalez ◽  
John G. Wood
Keyword(s):  
Acute Hypoxia ◽  
Leukotriene B4 ◽  
Ros Generation ◽  
Leukocyte Adherence ◽  
Systemic Hypoxia ◽  
Microvascular Alterations ◽  
Reactive Oxidant ◽  
Underlying Mechanisms ◽  
Mesenteric Microcirculation

Acute systemic hypoxia produces rapid leukocyte adherence in the rat mesenteric microcirculation, although the underlying mechanisms are not fully known. Hypoxia is known to increase reactive oxygen species (ROS) generation, which could result in formation of the lipid inflammatory mediator leukotriene B4 (LTB4). The goal of this study was to examine the role of LTB4 in hypoxia-induced microvascular alterations. Using intravital microscopy, we determined the effect of the LTB4 antagonist, LTB4-dimethyl amide (LTB4-DMA), on ROS generation and leukocyte adherence in mesenteric venules during hypoxia. Exogenous LTB4 increased ROS generation to 144 ± 8% compared with control values and also promoted leukocyte adherence. These responses to LTB4 were blocked by pretreating the mesentery with LTB4-DMA. Leukopenia did not significantly attenuate the LTB4-induced increase in ROS generation (142 ± 12.1%). LTB4-DMA substantially, though not completely, reduced hypoxia-induced ROS generation from 66 ± 18% to 11 ± 4% above control values. Hypoxia-induced leukocyte adherence was significantly attenuated by LTB4-DMA. Our results support a role for LTB4in the mechanism of hypoxia-induced ROS generation and leukocyte adherence in the rat mesenteric microcirculation.

scholarly journals A Novel Tetrapeptide Derivative Exhibits In Vitro Inhibition of Neutrophil-Derived Reactive Oxygen Species and Lysosomal Enzymes Release

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
Meera Ramanujam ◽  
Rengarajulu Puvanakrishnan
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Anion ◽  
Lysosomal Enzymes ◽  
Reactive Oxygen ◽  
Peptide Sequence ◽  
Ros Generation ◽  
Oxygen Species ◽  
Complement Factors

Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39–42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.

Extremely enhanced contaminant decomposition catalyzed by hemin via the coupling of persistent free radicals and ascorbic acid

2015 ◽  
Vol 51 (89) ◽  
pp. 16139-16142 ◽  
Author(s):  
Yuyuan Yao ◽  
Bin Jiang ◽  
Yajun Mao ◽  
Juan Chen ◽  
Zhenfu Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Ascorbic Acid ◽  
Free Radicals ◽  
Reactive Oxygen ◽  
Environmental Pollutant ◽  
Ros Generation ◽  
Oxygen Species ◽  
Positive Role ◽  
Rate Enhancement

A positive role of PFRs in enhancing reactive oxygen species (ROS) generation for an extreme rate enhancement in environmental pollutant decomposition is reported.

scholarly journals Silica particles cause NADPH oxidase–independent ROS generation and transient phagolysosomal leakage

2015 ◽  
Vol 26 (18) ◽  
pp. 3150-3164 ◽  
Author(s):  
Gaurav N. Joshi ◽  
Alexandra M. Goetjen ◽  
David A. Knecht
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Lung Fibrosis ◽  
Membrane Damage ◽  
Cell Types ◽  
Silica Particles ◽  
Ros Generation ◽  
Oxygen Species ◽  
Latex Particles

Chronic inhalation of silica particles causes lung fibrosis and silicosis. Silica taken up by alveolar macrophages causes phagolysosomal membrane damage and leakage of lysosomal material into the cytoplasm to initiate apoptosis. We investigated the role of reactive oxygen species (ROS) in this membrane damage by studying the spatiotemporal generation of ROS. In macrophages, ROS generated by NADPH oxidase 2 (NOX2) was detected in phagolysosomes containing either silica particles or nontoxic latex particles. ROS was only detected in the cytoplasm of cells treated with silica and appeared in parallel with an increase in phagosomal ROS, as well as several hours later associated with mitochondrial production of ROS late in apoptosis. Pharmacological inhibition of NOX activity did not prevent silica-induced phagolysosomal leakage but delayed it. In Cos7 cells, which do not express NOX2, ROS was detected in silica-containing phagolysosomes that leaked. ROS was not detected in phagolysosomes containing latex particles. Leakage of silica-containing phagolysosomes in both cell types was transient, and after resealing of the membrane, endolysosomal fusion continued. These results demonstrate that silica particles can generate phagosomal ROS independent of NOX activity, and we propose that this silica-generated ROS can cause phagolysosomal leakage to initiate apoptosis.

The role of ferroptosis in organ toxicity

2021 ◽  
pp. 096032712110529
Author(s):  
Fatemeh Yarmohammadi ◽  
A Wallace Hayes ◽  
Gholamreza Karimi
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Iron Chelators ◽  
Ros Generation ◽  
Oxygen Species ◽  
Organ Toxicity ◽  
Ros Accumulation ◽  
Dependent Form ◽  
Novel Therapeutic

Ferroptosis, an iron-dependent form of programmed cell death, is characterized by iron overload, increased reactive oxygen species (ROS) generation, and depletion of glutathione (GSH) and lipid peroxidation. Lipophilic antioxidants and iron chelators can prevent ferroptosis. GSH-dependent glutathione peroxidase 4 (GPX4) prevents lipid ROS accumulation. Ferroptosis is thought to be initiated through GPX4 inactivation. Moreover, mitochondrial iron overload derived from the degradation of ferritin is involved in increasing ROS generation. Ferroptosis has been suggested to explain the mechanism of action of organ toxicity induced by several drugs and chemicals. Inhibition of ferroptosis may provide novel therapeutic opportunities for treatment and even prevention of such organ toxicities.

Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats

2000 ◽  
Vol 89 (4) ◽  
pp. 1561-1568 ◽  
Author(s):  
John G. Wood ◽  
Jennifer S. Johnson ◽  
Leone F. Mattioli ◽  
Norberto C. Gonzalez
Keyword(s):  
Vascular Function ◽  
Microvascular Permeability ◽  
Hypoxic Exposure ◽  
Ros Generation ◽  
Leukocyte Adherence ◽  
Conscious Animal ◽  
Subsequent Decrease ◽  
Conflicting Evidence ◽  
Systemic Hypoxia

We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734–1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873–881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal.

In the idiopathic inflammatory myopathies (IIM), do reactive oxygen species (ROS) contribute to muscle weakness?

2015 ◽  
Vol 74 (7) ◽  
pp. 1340-1346 ◽  
Author(s):  
Adam P Lightfoot ◽  
Anne McArdle ◽  
Malcolm J Jackson ◽  
Robert G Cooper
Keyword(s):  
Reactive Oxygen Species ◽  
Muscle Weakness ◽  
Inflammatory Cell ◽  
Immune Cell ◽  
Ros Generation ◽  
Muscle Dysfunction ◽  
Idiopathic Inflammatory Myopathies ◽  
Oxygen Species ◽  
Inflammatory Myopathies

The idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune disorders, collectively known as myositis. Affected patients present with proximal muscle weakness, which usually improves following treatment with immunosuppressants, but often incompletely so, thus many patients remain weak. IIMs are characterised histologically by inflammatory cell infiltrates into skeletal muscle and overexpression of major histocompatibility complex I on muscle cell surfaces. Although inflammatory cell infiltrates represent a major feature of myositis there is growing evidence that muscle weakness correlates only poorly with the degree of cellular infiltration, while weakness may in fact precede such infiltrations. The mechanisms underpinning such non-immune cell mediated weakness in IIM are poorly understood. Activation of the endoplasmic reticulum stress pathways appears to be a potential contributor. Data from non-muscle cells indicate that endoplasmic reticulum stress results in altered redox homeostasis capable of causing oxidative damage. In myopathological situations other than IIM, as seen in ageing and sepsis, evidence supports an important role for reactive oxygen species (ROS). Modified ROS generation is associated with mitochondrial dysfunction, depressed force generation and activation of muscle catabolic and autophagy pathways. Despite the growing evidence demonstrating a key role for ROS in skeletal muscle dysfunction in myopathologies other than IIM, no research has yet investigated the role of modified generation of ROS in inducing the weakness characteristic of IIM. This article reviews current knowledge regarding muscle weakness in the absence of immune cells in IIM, and provides a background to the potential role of modified ROS generation as a mechanism of muscle dysfunction. The authors suggest that ROS-mediated mechanisms are potentially involved in non-immune cell mediated weakness seen in IIM and outline how these mechanisms might be investigated in this context. This appears a timely strategy, given recent developments in targeted therapies which specifically modify ROS generation.

Flumazenil preconditions cardiomyocytes via oxygen radicals and KATP channels

2000 ◽  
Vol 279 (4) ◽  
pp. H1858-H1863 ◽  
Author(s):  
Qiang Zhang ◽  
Zhenhai Yao
Keyword(s):  
Cell Death ◽  
Intracellular Signaling ◽  
Ventricular Myocytes ◽  
Katp Channels ◽  
Reduced Form ◽  
Ros Generation ◽  
Oxygen Species ◽  
Intracellular Signaling Pathway ◽  
Flow Through

We determined whether flumazenil mimics ischemic preconditioning in chick cardiomyocytes and examined the role of intracellular reactive oxygen species (ROS) and ATP-dependent potassium (KATP) channels in mediating the effect. Chick ventricular myocytes were perfused with a balanced salt solution in a flow-through chamber. Cell viability was quantified using propidium iodide, and ROS generation was assessed using the reduced form of 2′,7′-dichlorofluorescin (DCFH). Cells were exposed to 1 h of simulated ischemia and 3 h of reoxygenation. Preconditioning was initiated with 10 min of ischemia followed by 10 min of reoxygenation. Alternatively, flumazenil was added to the perfusate for 10 min and removed 10 min before the start of ischemia. Flumazenil (1 and 10 μM) and preconditioning reduced cell death [54 ± 5%, n = 3; 26 ± 4%, n = 6 ( P < 0.05); and 20 ± 2%, n = 6 (P < 0.05), respectively, vs. 57 ± 7%, n = 10, in controls] and increased DCFH oxidation (an index of ROS production) [0.35 ± 0.11, n = 3; 2.64 ± 0.69, n = 8 ( P < 0.05); and 2.46 ± 0.52, n = 6 ( P< 0.05), respectively, vs. 0.26 ± 0.05, n = 9, in controls]. Protection and increased ROS signals with flumazenil (10 μM) were abolished with the thiol reductant N-(2-mercaptopropionyl)-glycine (2-MPG, 800 μM), an antioxidant (cell death: 2-MPG + flumazenil, 55 ± 12%, n = 6; ROS signals: 2-MPG + flumazenil, 0.11 ± 0.19, n = 6). Treatment with 5-hydroxydecanoate (1 mM), a selective mitochondrial KATP channel antagonist, abolished its protection. These results demonstrate that flumazenil mimics preconditioning to reduce cell death in myocytes. ROS signals with the resultant mitochondrial KATP channel activation are important components of the intracellular signaling pathway of flumazenil.

scholarly journals MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines

2021 ◽  
Vol 22 (15) ◽  
pp. 8300
Author(s):  
Kazuo Tomita ◽  
Taisuke Nagasawa ◽  
Yoshikazu Kuwahara ◽  
Seiji Torii ◽  
Kento Igarashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Anticancer Agents ◽  
Mitochondrial Membrane ◽  
Ros Generation ◽  
Oxygen Species ◽  
H2o2 Treatment ◽  
Iron Storage ◽  
X Ray ◽  
Cox 2

In cancer therapy, radioresistance or chemoresistance cells are major problems. We established clinically relevant radioresistant (CRR) cells that can survive over 30 days after 2 Gy/day X-ray exposures. These cells also show resistance to anticancer agents and hydrogen peroxide (H2O2). We have previously demonstrated that all the CRR cells examined had up-regulated miR-7-5p and after miR-7-5p knockdown, they lost radioresistance. However, the mechanism of losing radioresistance remains to be elucidated. Therefore, we investigated the role of miR-7-5p in radioresistance by knockdown of miR-7-5p using CRR cells. As a result, knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+ amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount. H2O2 treatment after ALOX12 overexpression led to the enhancement of intracellular H2O2 amount and lipid peroxidation. By contrast, miR-7-5p knockdown seemed not to be involved in COX-2 and glycolysis signaling but affected the morphology of CRR cells. These results indicate that miR-7-5p control radioresistance via ROS generation that leads to ferroptosis.

scholarly journals Interaction between reactive oxygen species and nitric oxide in the microvascular response to systemic hypoxia

2002 ◽  
Vol 93 (4) ◽  
pp. 1411-1418 ◽  
Author(s):  
Dawn R. S. Steiner ◽  
Norberto C. Gonzalez ◽  
John G. Wood
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Leukocyte Adherence ◽  
No Donor ◽  
Substrate Limitation ◽  
Systemic Hypoxia ◽  
Microvascular Response ◽  
Spermine Nonoate

Systemic hypoxia results in oxidative stress due to a change in the reactive oxygen species (ROS)-nitric oxide (NO) balance. These experiments explored two mechanisms for the altered ROS-NO balance: 1) decreased NO synthesis by NO synthase due to limited O2 substrate availability and 2) increased superoxide generation. ROS levels and leukocyte adherence in mesenteric venules of rats during hypoxia were studied in the absence and presence of an NO donor [spermine NONOate (SNO)] and of the NO precursorl-arginine. We hypothesized that if the lower NO levels during hypoxia were due to O2 substrate limitation,l-arginine would not prevent hypoxia-induced microvascular responses. Graded hypoxia (produced by breathing 15, 10, and 7.5% O2) increased both ROS (123 ± 6, 148 ± 11, and 167 ± 3% of control) and leukocyte adherence. ROS levels during breathing of 10 and 7.5% O2 were significantly attenuated by SNO (105 ± 6 and 108 ± 3%, respectively) andl-arginine (117 ± 5 and 115 ± 2%, respectively). Both interventions reduced leukocyte adherence by similar degrees. The fact that the effects of l-arginine were similar to those of SNO does not support the idea that NO generation is impaired in hypoxia and suggests that tissue NO levels are depleted by the increased ROS during hypoxia.

Sign in / Sign up

Export Citation Format

Share Document