title: ET-1 mediates the release of reactive oxygen species and TNF-α in lung tissue by protein kinase C α and β1.
abstract: BACKGROUND
  The aim of this study was to determine the involvement of protein kinase C (PKC) in the ET-1 induced generation of reactive oxygen species and TNF-α in rat lungs.
  
  
  METHODS
  Experiments were performed on 6 groups of rats: Group I: saline-treated control; Group II: saline followed by endothelin-1 (ET-1) (3μg/kg); Group III: saline followed by selective PKC αβ1 inhibitor (Gö6976) (2μg/kg); Group IV: Gö6976 (2μg/kg) administered 30min before ET-1 (3μg/kg); Group V: saline followed by the PKC activator phorbol 12-myristate 13-acetate (PMA) (50μg/kg); Group VI: Gö6976 (2μg/kg) administered 30min before PMA (50μg/kg). After 5h, the animals were euthanized and their lungs were isolated for measurements.
  
  
  RESULTS
  ET-1 resulted in increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels and lung edema, as well as a decrease in GSH/GSSG ratio compared to the controls. The level of TNF-α also was elevated in the presence of ET-1. Administration of Gö6976 30min before ET-1 injection significantly decreased lung edema, as well as the concentrations of TBARS, H2O2 and TNF-α, but increased the GSH/GSSG redox ratio compared to ET-1. Conversely, PMA elevated lung edema and TBARS, H2O2 and TNF-α concentrations, but decreased the GSH/GSSG redox ratio compared to the control group. Treatment with Gö6976 significantly ameliorated the PMA-induced oxidative stress parameters, decreased tissue TNF-α level, and lung edema.
  
  
  CONCLUSIONS
  Endothelin-1 induces ROS generation, increases TNF-α level and lung edema via activation of PKC αβ1.
authors.affiliation: Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Łódź, Poland. Electronic address: anna.goraca@umed.lodz.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Gorąca
authors.affiliation: Department of Immunopathology, Faculty of Biomedical Sciences and Postgraduate Training, Medical University of Lodz, Łódź, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kleniewska
authors.affiliation: Department of Applied Pharmacy, Department of Pharmacy, Medical University of Lodz, Łódź, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Skibska
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000096:biosynthesis*
chemical_list: D019332:Endothelin-1; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; D051571:Protein Kinase C-alpha
keywords: Endothelin 1; Protein kinase C; Reactive oxygen species