Linked Life Data

16357365

Source:http://linkedlifedata.com/resource/pubmed/id/16357365

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-3-20
pubmed:abstractText
Lung capillary endothelial cells (ECs) are a critical target of oxygen toxicity and play a central role in the pathogenesis of hyperoxic lung injury. To determine mechanisms and time course of EC activation in normobaric hyperoxia, we measured endothelial concentration of reactive oxygen species (ROS) and cytosolic calcium ([Ca(2+)](i)) by in situ imaging of 2',7'-dichlorofluorescein (DCF) and fura 2 fluorescence, respectively, and translocation of the small GTPase Rac1 by immunofluorescence in isolated perfused rat lungs. Endothelial DCF fluorescence and [Ca(2+)](i) increased continuously yet reversibly during a 90-min interval of hyperoxic ventilation with 70% O(2), demonstrating progressive ROS generation and second messenger signaling. ROS formation increased exponentially with higher O(2) concentrations. ROS and [Ca(2+)](i) responses were blocked by the mitochondrial complex I inhibitor rotenone, whereas inhibitors of NAD(P)H oxidase and the intracellular Ca(2+) chelator BAPTA predominantly attenuated the late phase of the hyperoxia-induced DCF fluorescence increase after > 30 min. Rac1 translocation in lung capillary ECs was barely detectable at normoxia but was prominent after 60 min of hyperoxia and could be blocked by rotenone and BAPTA. We conclude that hyperoxia induces ROS formation in lung capillary ECs, which initially originates from the mitochondrial electron transport chain but subsequently involves activation of NAD(P)H oxidase by endothelial [Ca(2+)](i) signaling and Rac1 activation. Our findings demonstrate rapid activation of ECs by hyperoxia in situ and identify mechanisms that may be relevant in the initiation of hyperoxic lung injury.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
453-63
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16357365-Animals, pubmed-meshheading:16357365-Calcium, pubmed-meshheading:16357365-Capillaries, pubmed-meshheading:16357365-Electron Transport Complex I, pubmed-meshheading:16357365-Endothelial Cells, pubmed-meshheading:16357365-Endothelium, Vascular, pubmed-meshheading:16357365-Enzyme Activation, pubmed-meshheading:16357365-Fluoresceins, pubmed-meshheading:16357365-Fluorescent Dyes, pubmed-meshheading:16357365-Fura-2, pubmed-meshheading:16357365-Hyperoxia, pubmed-meshheading:16357365-Lung, pubmed-meshheading:16357365-Male, pubmed-meshheading:16357365-Microcirculation, pubmed-meshheading:16357365-NADPH Oxidase, pubmed-meshheading:16357365-Oxygen, pubmed-meshheading:16357365-Protein Transport, pubmed-meshheading:16357365-Rats, pubmed-meshheading:16357365-Rats, Sprague-Dawley, pubmed-meshheading:16357365-Reactive Oxygen Species, pubmed-meshheading:16357365-Signal Transduction, pubmed-meshheading:16357365-rac1 GTP-Binding Protein
pubmed:year
2006
pubmed:articleTitle
Hyperoxia-induced reactive oxygen species formation in pulmonary capillary endothelial cells in situ.
pubmed:affiliation
Institute of Physiology Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't