Superoxide Dismutases in the Lung and Human Lung Diseases

Kinnula, Vuokko L.; Crapo, James D.

doi:10.1164/rccm.200212-1479so

Cited by 544 publications

(432 citation statements)

References 282 publications

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“…All SODs are highly expressed in lung tissue, vessels, and airways (272). However, when their relative distribution is compared, the activities of CuZnSOD and MnSOD are lower in the lung compared with the other organs such as the liver, kidney, heart, and brain; whereas the EC-SOD activity has been reported to be much higher in the lung (217). The knockout mice deficient in CuZn SOD and EC-SOD are viable and show no abnormality associated with oxidative damage, indicating that other antioxidant enzymes compensate for their deficiency under normal physiological conditions (51, 475).…”

Section: Xo-derived Ros In Inflammationmentioning

confidence: 99%

Reactive Oxygen Species in Inflammation and Tissue Injury

Mittal

Siddiqui

Tran

et al. 2014

Antioxidants & Redox Signaling

3,606

2,424

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Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126-1167.

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Section: Xo-derived Ros In Inflammationmentioning

confidence: 99%

Reactive Oxygen Species in Inflammation and Tissue Injury

Mittal

Siddiqui

Tran

et al. 2014

Antioxidants & Redox Signaling

3,606

2,424

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“…antioxidants | cigarette smoke | chronic obstructive pulmonary disease | oxidants | glutathione E xtracellular superoxide dismutase (ECSOD or SOD3) is one of the three SOD antioxidant enzyme isoforms, and is highly expressed in lungs and vessels (1,2). It is located in the ECM, the junctions of airway epithelial cells, the surface of airway smooth muscle, and the lining of vessels of the lung.…”

mentioning

confidence: 99%

Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM

Yao

Arunachalam

Hwang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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175

166

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Extracellular superoxide dismutase (ECSOD or SOD3) is highly expressed in lungs and functions as a scavenger of O 2 • ─ . ECM fragmentation, which can be triggered by oxidative stress, participates in the pathogenesis of chronic obstructive pulmonary disease (COPD) through attracting inflammatory cells into the lungs. The level of SOD3 is significantly decreased in lungs of patients with COPD. However, the role of endogenous SOD3 in the development/progression of emphysema is unknown. We hypothesized that SOD3 protects against emphysema by attenuating oxidative fragmentation of ECM in mice. To test this hypothesis, SOD3-deficient, SOD3-transgenic, and WT C57BL/6J mice were exposed to cigarette smoke (CS) for 3 d (300 mg total particulate matter/m 3 ) to 6 mo (100 mg/m 3 total particulate matter) or by intratracheal elastase injection. Airspace enlargement, lung inflammation, lung mechanical properties, and exercise tolerance were determined at different time points during CS exposure or after elastase administration. CS exposure and elastase administration caused airspace enlargement as well as impaired lung function and exercise capacity in SOD3-null mice, which were improved in mice overexpressing SOD3 and by pharmacological SOD mimetic. These phenomena were associated with SOD3-mediated protection against oxidative fragmentation of ECM, such as heparin sulfate and elastin, thereby attenuating lung inflammatory response. In conclusion, SOD3 attenuates emphysema and reduces oxidative fragmentation of ECM in mouse lung. Thus, pharmacological augmentation of SOD3 in the lung may have a therapeutic potential in the intervention of COPD/emphysema.antioxidants | cigarette smoke | chronic obstructive pulmonary disease | oxidants | glutathione E xtracellular superoxide dismutase (ECSOD or SOD3) is one of the three SOD antioxidant enzyme isoforms, and is highly expressed in lungs and vessels (1, 2). It is located in the ECM, the junctions of airway epithelial cells, the surface of airway smooth muscle, and the lining of vessels of the lung. SOD3 functions as a superoxide anion scavenger, thereby attenuating oxidative stress, which may play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Acute loss of SOD3 in adult mice causes death, whereas low mortality rates are seen in SOD3-overexpressing animals exposed to hyperoxia, suggesting an essential role of SOD3 for survival (3,4). Accumulating evidence shows that SOD3 polymorphism is associated with a decline in lung function in rodents and humans, and susceptibility to COPD, which may be a result of alteration of its encoding protein structure, function, and level (5-14). However, it is unclear whether endogenous SOD3 participates in the development/ progression of the inflammatory response, leading to COPD/ emphysema.Cigarette smoke (CS) is the major etiological factor in the pathogenesis of COPD, which is characterized by chronic lung inflammation, parenchymal destruction (i.e., emphysema), and accelerated decline in lung function....

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“…The promoters of all SOD enzymes have been reported to contain glucocorticoid response elements. 39,40 Although there were no significant changes in either CuZnSOD or MnSOD expression (data not shown), hydrocortisone increased ecSOD protein expression by 71% AE 26% (P < 0.05; . PPHN FPASMC were exposed to 21% O 2 -5% CO 2 or 95% O 2 -5% CO 2 AE 100 nM HC for 24 hours, and total protein was harvested.…”

Section: Hydrocortisone Normalizes Hyperoxia-induced Pde5 Activity Inmentioning

confidence: 85%

Hydrocortisone Normalizes Phosphodiesterase‐5 Activity in Pulmonary Artery Smooth Muscle Cells from Lambs with Persistent Pulmonary Hypertension of the Newborn

et al. 2014

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Phosphodiesterase-5 (PDE5) is the primary phosphodiesterase in the pulmonary vasculature. It degrades cyclic guanosine monophosphate (cGMP) and inhibits cGMP-mediated vasorelaxation. We previously reported that hydrocortisone treatment decreased hyperoxia-induced PDE5 activity and markers of oxidative stress in lambs with persistent pulmonary hypertension of the newborn (PPHN) ventilated with 100% O 2 . The objective of our study was to determine the molecular mechanism by which hydrocortisone downregulates PDE5 and oxidative stress in fetal pulmonary artery smooth muscle cells (FPASMCs) from PPHN lambs. PPHN FPASMC were incubated for 24 hours in either 21% or 95% O 2 . Some cells were treated with 100 nM hydrocortisone and/or AE1 μM helenalin, an inhibitor of nuclear factor κ B (NFκB), a redox-sensitive transcription factor. Exposure to hyperoxia led to increased PDE5 activity, oxidative stress, and NFκB activity. Pretreatment of PPHN FPASMC with hydrocortisone normalized PDE5 activity, decreased cytosolic oxidative stress, increased expression of extracellular superoxide dismutase and NFκB inhibitory protein, and decreased NFκB activity. Similarly, treatment with NFκB inhibitor, helenalin, decreased PDE5 activity. These data suggest that hyperoxia activates NFκB, which in turn induces PDE5 activity in PPHN FPASMC, whereas treatment with hydrocortisone attenuates these changes by blocking reactive oxygen species-induced NFκB activity.

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Superoxide Dismutases in the Lung and Human Lung Diseases

Cited by 544 publications

References 282 publications

Reactive Oxygen Species in Inflammation and Tissue Injury

Reactive Oxygen Species in Inflammation and Tissue Injury

Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM

Hydrocortisone Normalizes Phosphodiesterase‐5 Activity in Pulmonary Artery Smooth Muscle Cells from Lambs with Persistent Pulmonary Hypertension of the Newborn

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