Evidence Against the Involvement of Multiple Radical Generating Sites in the Expression of the Vascular Cell Adhesion Molecule-1

Pietersma, Anneke; Jong, N. de; Wit, L. Elly A. de; Kraakslee, Regina; Koster, J.F.; Sluiter, Wim J.

doi:10.3109/10715769809065800

Cited by 20 publications

(15 citation statements)

References 27 publications

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“…These results are consistent with CYP450-derived ROS, not NADPH-derived oxidants, as essential intermediates in TNF-␣-stimulated expression of MAdCAM-1. With respect to cytokine signaling, our data corroborate and extend findings by Pietersma et al (27), who stated that NADPH oxidase-derived ROS do not appear to contribute to cytokine induction of adhesion molecules in human umbilical vein endothelial cells (HUVEC). Rather, they suggested that cytokine-induced ECAM expression was due to oxidants formed by CYP450 activity.…”

Section: Discussionsupporting

confidence: 95%

“…Several prior studies have suggested that a phagocyte-type NADPH oxidase, existing within endothelial cells, might be an important source of signal oxidants (1,12,14,22). Cytochrome P-450 (CYP450) monooxygenases have also recently been proposed as another source of intracellular signaling ROS (8,27,30). Therefore, in the current study we compared the contributions of endothelial NADPH oxidase and CYP450 monooxygenase-derived oxidants in TNF-␣-induced expression of ECAMs.…”

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confidence: 94%

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TNF-α-induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent

Sasaki

Ostanin

Elrod

et al. 2003

American Journal of Physiology-Cell Physiology

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It is strongly suspected that cytokine-induced gene expression in inflammation is oxidant mediated; however, the intracellular sources of signaling oxidants remain controversial. In inflammatory bowel disease (IBD) proinflammatory cytokines, such as TNF-alpha, trigger gene expression of endothelial adhesion molecules including mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 plays an essential role in gut inflammation by governing the infiltration of leukocytes into the intestine. Several groups suggest that endothelial-derived reduced NADP (NADPH) oxidase produces signaling oxidants that control the expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1). In addition to NADPH oxidase, cytochrome P-450 (CYP450) monooxygenases have also been shown to trigger cytokine responses. We found that in high endothelial venular cells (SVEC4-10), multiple inhibitors of CYP450 monooxygenases (SKF-525a, ketoconazole, troleandomycin, itraconazole) attenuated TNF-alpha induction of MAdCAM-1, whereas NADPH oxidase inhibition (PR-39) did not. Conversely, E-selectin, ICAM-1, and VCAM-1 induction requires both NADPH oxidase and CYP450-derived oxidants. We show here that MAdCAM-1 induction may depend exclusively on CYP450-derived oxidants, suggesting that CYP450 blockers might represent a possible novel therapeutic treatment for human IBD.

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Section: Discussionsupporting

confidence: 95%

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confidence: 94%

TNF-α-induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent

Sasaki

Ostanin

Elrod

et al. 2003

American Journal of Physiology-Cell Physiology

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“…The concentration of H 2 O 2 added to the media of our cell culture experiments (100 μM) may exceed the radical scavenging abilities of this compound, resulting in an inability to prevent the damaging lipid modifications that occur with high levels of oxidants. In addition, previous studies suggest that apocynin’s antioxidant properties are conveyed through inhibiting H 2 O 2 signaling interactions, including cytochrome-P450 (32), thromboxane synthase inhibition (33), the synthesis of the endogenous antioxidant GSH (34), and the inhibition of H 2 O 2 -induced p38 mitogen-activated protein kinase, Akt, and extracellular regulated kinase 1/2 activity (10). Further, our in vivo data demonstrate that apocynin may also serve as an antioxidant in the diaphragm during MV through the maintenance of higher levels of the endogenous antioxidants, GSH and GSH peroxidase.…”

Section: Discussionmentioning

confidence: 99%

Apocynin attenuates diaphragm oxidative stress and protease activation during prolonged mechanical ventilation

McClung

Gammeren

Whidden

et al. 2009

Critical Care Medicine

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Objective-To investigate whether apocynin protects the diaphragm from wasting and oxidative stress during mechanical ventilation (MV).Design-Prospective, randomized, controlled study. Setting-Research laboratory. Subjects-Adult female Sprague-Dawley rats.Interventions-Rats were randomly assigned to one of five experimental groups: 1) acutely anesthetized control, 2) spontaneous breathing control, 3) spontaneously breathing control with administration of the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin, 4) mechanically ventilated, and 5) mechanically ventilated with apocynin. Measurements and MainResults-Apocynin attenuated MV-induced diaphragmatic oxidative stress, contractile dysfunction, and type I, type IIa, and type IIb/IIx myofiber atrophy. The apocynin-induced attenuation of MV-induced diaphragmatic atrophy and contractile dysfunction occurred in conjunction with a reduction in the small increase in nicotinamide adenine dinucleotide phosphate oxidase activity as well as the preservation of total glutathione levels, glutathione peroxidase protein abundance, and a decrease in the activation of the cysteine proteases, calpain-1 and caspase-3. Interestingly, independent of MV, apocynin increased diaphragmatic levels of calpastatin, an endogenous calpain inhibitor. Furthermore, treatment of skeletal muscle cells in culture (C2C12 myotubes) with apocynin resulted in an increase in both calpastatin mRNA levels and protein abundance.Conclusions-Our results suggest that the protective effects of apocynin on the diaphragm during prolonged MV seem to be linked to both its functions as an antioxidant and role in cellular signaling regulating the cysteine protease inhibitor calpastatin.Keywords skeletal muscle; NADPH oxidase; protease; atrophy; oxidative stress; antioxidantThe first two authors contributed equally to this work.The authors have not disclosed any potential conflicts of interest.For information regarding this article, joseph.mcclung@duke.edu NIH Public Access Author ManuscriptCrit Care Med. Author manuscript; available in PMC 2010 July 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMechanical ventilation (MV) is used to maintain adequate alveolar ventilation in patients who are incapable of doing so on their own. Evidence indicates that MV-induced oxidative stress in the diaphragm is a major contributor to diaphragmatic atrophy and contractile dysfunction (1,2) and leads to difficulties in removing patients from the ventilator (i.e., "weaning"). Therefore, circumventing reactive oxygen species (ROS) generation or enhancing the free radical scavenging capabilities of the diaphragm via the administration of antioxidant compounds possesses exciting potential for protecting the diaphragm during MV.Our laboratory and others have suggested that oxidative stress is a critical upstream signaling event leading to the activation of cysteine proteases (i.e., calpains and caspases) involved in myofilament disassembly as well as the deactivation of endo...

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“…Apocynin, a methoxy-substituted catechol, blocks phagocytic NADPH oxidase in neutrophils (13,57) and macrophages (40,57) as well as systemic endothelial NADPH oxidase activity (26) through inhibition of p47 phox translocation (39). Other actions include inhibition of thromboxane synthase (13) and cytochrome P450 (48). Additional experiments were performed with diphenyleneiodonium (DPI), which impairs NADPH oxidase by flavoprotein inhibition (15).…”

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confidence: 99%

Effect of NADPH oxidase inhibition on cardiopulmonary bypass-induced lung injury

Dodd‐o

Welsh

Salazar

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Effect of NADPH oxidase inhibition on cardiopulmonary bypass-induced lung injury. Am J Physiol Heart Circ Physiol 287: H927-H936, 2004; 10.1152/ajpheart.01138.2003.-Cardiopulmonary bypass (CPB) causes acute lung injury. Reactive oxygen species (ROS) from NADPH oxidase may contribute to this injury. To determine the role of NADPH oxidase, we pretreated pigs with structurally dissimilar NADPH oxidase inhibitors. Low-dose apocynin (4-hydroxy-3-methoxy-acetophenone; 200 mg/kg, n ϭ 6), highdose apocynin (400 mg/kg, n ϭ 6), or diphenyleneiodonium (DPI; 8 mg/kg) was compared with diluent (n ϭ 8). An additional group was treated with indomethacin (10 mg/kg, n ϭ 3). CPB was performed for 2 h with deflated lungs, complete pulmonary artery occlusion, and bronchial artery ligation to maximize lung injury. Parameters of pulmonary function were evaluated for 25 min following CPB. Blood chemiluminescence indicated neutrophil ROS production. Electron paramagnetic resonance determined the effect of apocynin and DPI on in vitro pulmonary endothelial ROS production following hypoxiareoxygenation. Both apocynin and DPI attenuated blood chemiluminescence and post-CPB hypoxemia. At 25 min post-CPB with FI O 2 ϭ 1, arterial PO2 (PaO 2 ) averaged 52 Ϯ 5, 162 Ϯ 54, 335 Ϯ 88, and 329 Ϯ 119 mmHg in control, low-dose apocynin, high-dose apocynin, and DPI-treated groups, respectively (P Ͻ 0.01). Indomethacin had no effect. PaO 2 correlated with blood chemiluminescence measured after drug administration before CPB (R ϭ Ϫ0.60, P Ͻ 0.005). Neither apocynin nor DPI prevented the increased tracheal pressure, plasma cytokine concentrations (tumor necrosis factor-␣ and IL-6), extravascular lung water, and pulmonary vascular protein permeability observed in control pigs. NADPH oxidase inhibition, but not xanthine oxidase inhibition, significantly blocked endothelial ROS generation following hypoxia-reoxygenation (P Ͻ 0.05). NADPH oxidase-derived ROS contribute to the severe hypoxemia but not to the increased cytokine generation and pulmonary vascular protein permeability, which occur following CPB. diphenyleneiodonium; apocynin; reflection coefficient; pig; endothelium; hypoxia-reoxygenation; tumor necrosis factor; interleukin-6 CARDIOPULMONARY BYPASS (CPB) causes significant lung injury characterized by abnormal gas exchange and pulmonary edema (61). Pulmonary dysfunction results in a mortality rate of nearly 0.7% following cardiac surgery (12, 28), accounting for over half of the 1.3% overall mortality associated with this procedure (11). Proposed mechanisms behind CPB-induced lung injury include the adverse effects of pulmonary vascular ischemia and reperfusion (18), and, if the lung is deflated during CPB, tissue hypoxia and reoxygenation (18, 33). The generation of reactive oxygen species (ROS) is common to all of these injurious mechanisms and is thought to play an important role in the ensuing injury. Sources of ROS include activated inflammatory cells, such as neutrophils (44) and macrophages, as well as vascular endothelial cells subject...

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Evidence Against the Involvement of Multiple Radical Generating Sites in the Expression of the Vascular Cell Adhesion Molecule-1

Cited by 20 publications

References 27 publications

TNF-α-induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent

TNF-α-induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent

Apocynin attenuates diaphragm oxidative stress and protease activation during prolonged mechanical ventilation

Effect of NADPH oxidase inhibition on cardiopulmonary bypass-induced lung injury

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