Linked Life Data

9700086

Source:http://linkedlifedata.com/resource/pubmed/id/9700086

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Pt 1
pubmed:dateCreated
1998-9-16
pubmed:abstractText
Asbestos fibers are an important cause of lung fibrosis; however, the biological mechanisms are incompletely understood. The lung epithelium serves an important barrier function in the lung, and disrupting the epithelial barrier can contribute to lung fibrosis. Lung epithelial permeability is increased in patients with asbestosis, and asbestos fibers increase permeability across cultured human lung epithelium. However, the mechanism of this increased permeability is not known. Many of the biological effects of asbestos are postulated to be due to its ability to generate oxidants, and oxidants are known to increase epithelial permeability. However, we previously reported that altering the iron content of asbestos (important in oxidant generation) had no effect on its ability to increase permeability. For that reason, we undertook these studies to determine whether asbestos increases epithelial permeability through nonoxidant pathways. Both extracellular (H2O2) and intracellular (menadione) oxidants increase paracellular permeability across human lung epithelial monolayers. Extracellular catalase but not superoxide dismutase prevented increased permeability after both oxidant exposures. However, catalase offered no protection from asbestos-induced permeability. We next depleted the cells of glutathione or catalase to determine whether depleting normal cellular antioxidants would increase the sensitivity to asbestos. Permeability was the same in control cells and in cells depleted of these antioxidants. In addition to generating oxidants, asbestos also activates signal transduction pathways. Blocking protein kinase C activation did not prevent asbestos-induced permeability; however, blocking tyrosine kinase with tyrophostin A25 did prevent asbestos-induced permeability, and blocking tyrosine phosphatase with sodium vanadate enhanced the effect of asbestos. These data demonstrate that asbestos may increase epithelial permeability through nonoxidant pathways that involve tyrosine kinase activation. This model offers an important system for studying pathways involved in regulating lung epithelial permeability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L262-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9700086-Amitrole, pubmed-meshheading:9700086-Asbestos, Amosite, pubmed-meshheading:9700086-Asbestos, Serpentine, pubmed-meshheading:9700086-Buthionine Sulfoximine, pubmed-meshheading:9700086-Catalase, pubmed-meshheading:9700086-Cell Membrane Permeability, pubmed-meshheading:9700086-Cells, Cultured, pubmed-meshheading:9700086-Epithelial Cells, pubmed-meshheading:9700086-Glutathione, pubmed-meshheading:9700086-Humans, pubmed-meshheading:9700086-Hydrogen Peroxide, pubmed-meshheading:9700086-Kinetics, pubmed-meshheading:9700086-Lung, pubmed-meshheading:9700086-Mannitol, pubmed-meshheading:9700086-Oxidants, pubmed-meshheading:9700086-Phorbol 12,13-Dibutyrate, pubmed-meshheading:9700086-Pulmonary Fibrosis, pubmed-meshheading:9700086-Time Factors, pubmed-meshheading:9700086-Vitamin K
pubmed:year
1998
pubmed:articleTitle
Asbestos-induced lung epithelial permeability: potential role of nonoxidant pathways.
pubmed:affiliation
Division of Pulmonary, Critical Care and Occupational Medicine, Department of Medicine, University of Iowa, Iowa City, Iowa 52240, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't