Increased Focal Adhesion Kinase- and Urokinase-type Plasminogen Activator Receptor-associated Cell Signaling in Endothelial Cells Exposed to Asbestos

Details

• Journal Article:
  Environmental Health Perspectives
• Personal Author:
  Barchowsky, A. ; Lannon, B. M. ; Elmore, L. C. ; Treadwell, M. D.
• Description:
  Porcine endothelial cells isolated from fresh aortas and third passage human pulmonary microvascular endothelial cells were incubated with chrysotile (12001295) or crocidolite (12001284) asbestos or RCF-1 ceramic fibers. A 1 to 3 hour exposure to 5mg/cm2 of chrysotile caused marked cell elongation and motility. When cells were pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI) anchored receptors or with herbimycin-A to inhibit tyrosine-kinase activity, little morphological change was noted when chrysotile was added. Affinity purification of GPI anchored urokinase type plasminogen activator receptor from chrysotile exposed cells indicated that asbestos altered the profile of proteins and phosphoprotein complexes with this receptor. Asbestos exposure also increased tyrosine-kinase activities in the complexes. Both chrysotile and crocidolite asbestos increased kinase activities associated with p60 Src or p120 focal adhesion kinase (FAK) factor as indicated by immunoprecipitations with selective monoclonal antibodies. Chrysotile also changed the profile of proteins and phosphoproteins associated with FAK in intact cells. The authors suggest that asbestos initiates endothelial cell phenotypic change through interactions with urokinase type plasminogen activator receptor containing complexes and that this change is mediated through tyrosine kinase cascades. [Description provided by NIOSH]
• Subjects:
  Animals Asbestos Carcinogens Cell Adhesion Endothelium Enzymes Gene Expression Regulation Inorganic Chemicals Lung Occupational Health Protein-Tyrosine Kinases Respiratory System Respiratory Tract Diseases Safety Signal Transduction Swine

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• Keywords:
  NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Asbestos-fibers; Carcinogens; Enzyme-activity; Lung-cells; Mammalian-cells; In-vitro-studies
• Source:
  Environ Health Perspect 1997 Sep; 105(Suppl 5):1131-1137
• ISSN:
  0091-6765
• Pubmed ID:
  9400712
• Pubmed Central ID:
  PMC1470137
• Document Type:
  Text
• Funding:
  ES07373/ES/NIEHS NIH HHS/United States ; HL52738/HL/NHLBI NIH HHS/United States ; OH03267/OH/NIOSH CDC HHS/United States
• Genre:
  Journal Article
• Place as Subject:
  New Hampshire ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  7 pdf pages
• Volume:
  105
• NIOSHTIC Number:
  nn:00239915
• Contact Point Address:
  Pharmacology and Toxicology Dartmouth Medical School Remsen 7650 Hanover, NH 03755-3835
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Chrysotile (CAS RN 12001-29-5) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  1997
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  Dartmouth College, Hanover, New Hampshire
• Peer Reviewed:
  True
• Collection(s):
  National Institute for Occupational Safety and Health CDC Public Access
• Main Document Checksum:
  urn:sha-512:bbc7073c6fdcd5190acda6ce10c3aaa2668ab02b331bec8071b10769b9ad10dd178738d982aad883e92c2ac15cfc7cb6fbfb4c4e06b6721673434b1c5672c173
• Download URL:
  https://stacks.cdc.gov/view/cdc/30764/cdc_30764_DS1.pdf
• File Type:
  [PDF - 2.31 MB ]