Linked Life Data

19833721

Source:http://linkedlifedata.com/resource/pubmed/id/19833721

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2009-12-7
pubmed:abstractText
Reactive oxygen species (ROS) generation, particularly by the endothelial NADPH oxidase family of proteins, plays a major role in the pathophysiology associated with lung inflammation, ischemia/reperfusion injury, sepsis, hyperoxia, and ventilator-associated lung injury. We examined potential regulators of ROS production and discovered that hyperoxia treatment of human pulmonary artery endothelial cells induced recruitment of the vesicular regulator, dynamin 2, the non-receptor tyrosine kinase, c-Abl, and the NADPH oxidase subunit, p47(phox), to caveolin-enriched microdomains (CEMs). Silencing caveolin-1 (which blocks CEM formation) and/or c-Abl expression with small interference RNA inhibited hyperoxia-mediated tyrosine phosphorylation and association of dynamin 2 with p47(phox) and ROS production. In addition, treatment of human pulmonary artery endothelial cells with dynamin 2 small interfering RNA or the dynamin GTPase inhibitor, Dynasore, attenuated hyperoxia-mediated ROS production and p47(phox) recruitment to CEMs. Using purified recombinant proteins, we observed that c-Abl tyrosine-phosphorylated dynamin 2, and this phosphorylation increased p47(phox)/dynamin 2 association (change in the dissociation constant (K(d)) from 85.8 to 6.9 nm). Furthermore, exposure of mice to hyperoxia increased ROS production, c-Abl activation, dynamin 2 association with p47(phox), and pulmonary leak, events that were attenuated in the caveolin-1 knock-out mouse confirming a role for CEMs in ROS generation. These results suggest that hyperoxia induces c-Abl-mediated dynamin 2 phosphorylation required for recruitment of p47(phox) to CEMs and subsequent ROS production in lung endothelium.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34964-75
pubmed:dateRevised
2010-12-14
pubmed:meshHeading
pubmed-meshheading:19833721-Animals, pubmed-meshheading:19833721-Bronchoalveolar Lavage Fluid, pubmed-meshheading:19833721-Caveolin 1, pubmed-meshheading:19833721-Cells, Cultured, pubmed-meshheading:19833721-Dynamin II, pubmed-meshheading:19833721-Endothelial Cells, pubmed-meshheading:19833721-Enzyme Activation, pubmed-meshheading:19833721-Humans, pubmed-meshheading:19833721-Hyperoxia, pubmed-meshheading:19833721-Lung, pubmed-meshheading:19833721-Male, pubmed-meshheading:19833721-Membrane Microdomains, pubmed-meshheading:19833721-Mice, pubmed-meshheading:19833721-Mice, Inbred C57BL, pubmed-meshheading:19833721-Mice, Knockout, pubmed-meshheading:19833721-NADPH Oxidase, pubmed-meshheading:19833721-Proto-Oncogene Proteins c-abl, pubmed-meshheading:19833721-RNA, Small Interfering, pubmed-meshheading:19833721-Reactive Oxygen Species
pubmed:year
2009
pubmed:articleTitle
Dynamin 2 and c-Abl are novel regulators of hyperoxia-mediated NADPH oxidase activation and reactive oxygen species production in caveolin-enriched microdomains of the endothelium.
pubmed:affiliation
Department of Medicine, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637, USA. psinglet@medicine.bsd.uchicago.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural