Involvement of Akt and endothelial nitric oxide synthase in ventilation-induced neutrophil infiltration: a prospective, controlled animal experiment

Li, Lifu; Liao, Shuen‐Kuei; Lee, Cheng-Huei; Huang, Chung-Chi; Quinn, Deborah A.

doi:10.1186/cc6101

Cited by 31 publications

(24 citation statements)

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“…The superoxide radicals react rapidly with NO generated by eNOS and form more potent oxidizing reactive nitrogen species such as peroxynitrite. eNOS plays an important role in the formation of peroxynitrite in endothelial cells during hyperoxia (9,10). Inhibition of eNOS using L-NAME or knock-out of eNOS reduces peroxynitrite-mediated cytotoxicity in hyperoxic retinal damage (9,11).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have suggested that endothelial nitric-oxide synthase (eNOS) plays an important role in the pathogenesis of oxygen toxicity (8,9). It has been reported that hyperoxia increases eNOS activity and nitric oxide (NO) release from endothelial cells (9,10). Inhibition of eNOS using L-NAME or knock-out of eNOS reduces peroxynitrite-mediated cytotoxicity in hyperoxic cellular damage in retina (9,11).…”

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confidence: 99%

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eNOS-β-Actin Interaction Contributes to Increased Peroxynitrite Formation during Hyperoxia in Pulmonary Artery Endothelial Cells and Mouse Lungs

Kondrikov

Elms

Fulton

et al. 2010

Journal of Biological Chemistry

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Oxygen toxicity is the most severe side effect of oxygen therapy in neonates and adults. Pulmonary damage of oxygen toxicity is related to the overproduction of reactive oxygen species (ROS). In the present study, we investigated the effect of hyperoxia on the production of peroxynitrite in pulmonary artery endothelial cells (PAEC) and mouse lungs. Incubation of PAEC under hyperoxia (95% O 2 ) for 24 h resulted in an increase in peroxynitrite formation. Uric acid, a peroxynitrite scavenger, prevented hyperoxia-induced increase in peroxynitrite. The increase in peroxynitrite formation is accompanied by increases in nitric oxide (NO) release and endothelial NO synthase (eNOS) activity. We have previously reported that association of eNOS with ␤-actin increases eNOS activity and NO production in lung endothelial cells. To study whether eNOS-␤-actin association contributes to increased peroxynitrite production, eNOS-␤-actin interaction were inhibited by reducing ␤-actin availability or by using a synthetic peptide (P326TAT) containing a sequence corresponding to the actin binding site on eNOS. We found that disruption of eNOS-␤-actin interaction prevented hyperoxia-induced increases in eNOS-␤-actin association, eNOS activity, NO and peroxynitrite production, and protein tyrosine nitration. Hyperoxia failed to induce the increases in eNOS activity, NO and peroxynitrite formation in COS-7 cells transfected with plasmids containing eNOS mutant cDNA in which amino acids leucine and tryptophan were replaced with alanine in the actin binding site on eNOS. Exposure of mice to hyperoxia resulted in significant increases in eNOS-␤-actin association, eNOS activity, and protein tyrosine nitration in the lungs. Our data indicate that increased association of eNOS with ␤-actin in PAEC contributes to hyperoxia-induced increase in the production of peroxynitrite which may cause nitrosative stress in pulmonary vasculature.Oxygen therapy is an important element of the management of various conditions such as adult or neonatal respiratory distress syndrome, circulatory shock, infection, multiple-organ failure syndrome, and pulmonary hypertension (1-6). However, prolonged exposure to increased concentrations of oxygen induces diffuse pulmonary injuries, excessive inflammation, and lung fibrosis. The hyperoxia-induced damages to lung cells have been attributed to the generation of reactive oxygen species (ROS) 2 and subsequent formation of more potent oxidants such as peroxynitrite (ONOO Ϫ ) (7,8). Several studies have suggested that endothelial nitric-oxide synthase (eNOS) plays an important role in the pathogenesis of oxygen toxicity (8, 9). It has been reported that hyperoxia increases eNOS activity and nitric oxide (NO) release from endothelial cells (9, 10). Inhibition of eNOS using L-NAME or knock-out of eNOS reduces peroxynitrite-mediated cytotoxicity in hyperoxic cellular damage in retina (9, 11). However, the mechanism for hyperoxia-induced increases in eNOS activity and NO release has not been clarified. In the present study,...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

eNOS-β-Actin Interaction Contributes to Increased Peroxynitrite Formation during Hyperoxia in Pulmonary Artery Endothelial Cells and Mouse Lungs

Kondrikov

Elms

Fulton

et al. 2010

Journal of Biological Chemistry

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“…Examination of the literature reveals that increased Akt activity has previously been correlated with LPS and ventilation induced lung injury, and associated with neutrophil migration to the affected region (Li et al ., 2007;Wang et al ., 2006). Notably, upregulation of Akt phosporylation at serine 473 was the initial event we observed following exposure to particulate Cr(VI).…”

Section: Discussionmentioning

confidence: 99%

Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium

Beaver

Stemmy

Constant

et al. 2009

Toxicology and Applied Pharmacology

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Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0–24 hours) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis.

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“…The superoxide radicals react with NO generated by eNOS and form more potent oxidizing reactive nitrogen species such as peroxynitrite. eNOS plays an important role in peroxynitrite formation and protein tyrosine nitration in endothelial cells during hyperoxia (4,9,21). L-Arginine, a substrate for NOS, enhances injury in the isolated rabbit lung during hyperoxia (22).…”

Section: Discussionmentioning

confidence: 99%

Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation

Kondrikov

Groß

Black

et al. 2014

Journal of Biological Chemistry

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Background: Hyperoxia increases NO and peroxynitrite in lung endothelium via increased interaction of eNOS with ␤-actin. Results: P326TAT with sequence corresponding to actin binding region of eNOS residues 326 -333 inhibited hyperoxiainduced disruption of endothelial barrier and apoptosis in cell culture and animal model. Conclusion: P326TAT ameliorates barrier dysfunction of hyperoxic lung endothelium and pulmonary edema. Significance: P326TAT can be a novel therapeutic agent to treat acute hyperoxic lung injury.

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Involvement of Akt and endothelial nitric oxide synthase in ventilation-induced neutrophil infiltration: a prospective, controlled animal experiment

Cited by 31 publications

References 32 publications

eNOS-β-Actin Interaction Contributes to Increased Peroxynitrite Formation during Hyperoxia in Pulmonary Artery Endothelial Cells and Mouse Lungs

eNOS-β-Actin Interaction Contributes to Increased Peroxynitrite Formation during Hyperoxia in Pulmonary Artery Endothelial Cells and Mouse Lungs

Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium

Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation

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