title: Increased localization and substrate activation of protein kinase C delta in lung epithelial cells following exposure to asbestos.
abstract: The protein kinase C (PKC) family consists of several isozymes whose substrates may be necessary for the regulation of key cellular events important in the pathogenesis of proliferative diseases. Asbestos is a carcinogen and fibroproliferative agent in lung that may cause cell signaling events through activation of PKC. Here we used a murine inhalation model of asbestos-induced inflammation and fibrosis to examine immunoreactivity of PKC delta and its substrate, phosphorylated-adducin (p-adducin), in cells of the lung. Moreover, we characterized PKC delta and p-adducin expression in a pulmonary epithelial cell line (C10) in both log versus confluent cells and in cells after mechanical wounding or crocidolite asbestos exposure. Both PKC delta and p-adducin were almost exclusively expressed in bronchiolar and alveolar type II (ATII) epithelial cells in lung sections and increased in these cell types after inhalation of asbestos by mice. Increases in membrane and nuclear localization of PKC delta were seen in log phase as compared to confluent C10 cells. Moreover, enhanced immunoreactivity of PKC delta was observed in epithelial cells expressing proliferating cell nuclear antigen (PCNA) after mechanical wounding or exposure to asbestos fibers. These studies show that activated PKC delta in pulmonary epithelial cells is a consequence of inhalation of asbestos and may be linked to the activation of cell proliferation.
authors.affiliation: Department of Pharmacology, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lounsbury
authors.forename: Maria
authors.initials: M
authors.lastname: Stern
authors.forename: Douglas
authors.initials: D
authors.lastname: Taatjes
authors.forename: Susan
authors.initials: S
authors.lastname: Jaken
authors.forename: Brooke T
authors.initials: BT
authors.lastname: Mossman
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001194:Asbestos / Q000008:administration & dosage / Q000633:toxicity*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007527:Isoenzymes / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000099291:Adducins
chemical_list: D001194:Asbestos; D002148:Calmodulin-Binding Proteins; D007527:Isoenzymes; D018809:Proliferating Cell Nuclear Antigen; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000099291:Adducins; C497259:Prkcd protein, mouse