Differential Induction of C-Fos, C-Jun, and Apoptosis in Lung Epithelial Cells Exposed to ROS or RNS

Details

• Personal Author:
  Janssen YM ; Matalon S ; Mossman BT
• Description:
  Induction of c-fos and c-jun gene expression and apoptosis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) in lung epithelial cells was demonstrated. RLE-6TN cells, a rat lung type II epithelial cell line, were exposed to 0 to 1 millimolar (mM) hydrogen-peroxide (7722841), nitric-oxide (10102439), or peroxynitrite (26404660) for 2 hours. Peroxynitrite was produced exogenously by reacting hydrogen-peroxide with sodium-nitrite or generated in-situ from 3-morpholinosydnonimine. Nitric-oxide was generated in-situ from spermine-1,3-propanediamine-N-(4-(1-(3- aminopropyl)-2- hydroxy-2-nitrosohydrazino)-butyl) or from S-nitro-N- acetylpenicillamine. The RNA was extracted from some cells and the level of expression of c-fos and c-jun mRNA was determined by Northern blotting. The concentrations of c-fos and c-jun proteins was determined by Western blotting. The extent of binding of activator-protein-1-transcription-factor (AP-1-TF) to AP-1 consensus DNA sequences was measured by an electrophoresis mobility shift assay. Induction of apoptosis was evaluated by a flow cytometric assay based on identifying cells with hypodiploid DNA and by a DNA laddering assay. Nitric-oxide and hydrogen-peroxide significantly increased the level of c-fos and c-jun mRNA expression, c-fos and c- jun protein concentrations, level of AP-1-TF binding to AP-1 consensus DNA sequences, and cellular apoptosis. Peroxynitrite applied exogenously to the cells or that was generated in-situ had no significant effect on these parameters. The authors conclude that nitric-oxide or hydrogen-peroxide increases early response gene expression leading to apoptosis in lung epithelial cells. Peroxynitrite did not cause these effects. Induction of c-fos and c- jun transcripts by ROS and RNS may play a critical role in the development of pulmonary diseases which are associated with reactive metabolites. [Description provided by NIOSH]
• Subjects:
  Genetics Hydrogen Peroxide Lung Nitrogen Oxides Occupational Health Peroxides Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Nitric Oxide Cell-damage Hydrogen Peroxide In-vitro-studies Lung-cells Lung Epithelium NIOSH-Grant NIOSH-Publication Nitrogen-oxides Nucleic-acids Oxidative-processes Peroxynitrite Pulmonary-system-disorders Reactive Nitrogen Species Reactive Oxygen Species

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 1 ; Vermont
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  273
• Issue:
  4
• NIOSHTIC Number:
  nn:00241854
• Citation:
  Am J Physiol Lung Cell Mol Physiol 1997 Oct; 273(4):L789-L796
• Contact Point Address:
  Yvonne M. W. Janssen, Department of Pathology, University of Vermont, Burlington, Vermont 05405
• CAS Registry Number:
  Hydrogen peroxide (CAS RN 7722-84-1) ; Nitric oxide (CAS RN 10102-43-9) ; Peroxynitric acid (CAS RN 26404-66-0)
• Federal Fiscal Year:
  1998
• Performing Organization:
  Pathology University of Vermont Medical Alumni Bldg a 249 Burlington, VT 05405-0068
• Peer Reviewed:
  True
• Start Date:
  19970401
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20000331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b3b2e8c4cb176048fc67c9daa91b6c54e4527ee23479870a155d971e44d7fb8edf713a11c6b25a3b45d07527bc392493a7e09cde2d32f48c72a60b17689374f2
• Download URL:
  https://stacks.cdc.gov/view/cdc/198128/cdc_198128_DS1.pdf
• File Type:
  [PDF - 754.44 KB ]