title: Differential effects of oxidative stress on hepatic endothelial and Kupffer cell eicosanoid release in response to endothelin-1.
abstract: OBJECTIVE
  The vasoconstrictor endothelin-1 can induce vasomodulators release like nitric oxide in the liver. Here the authors explored whether endothelin-1 can stimulate endothelial and Kupffer cells release of other vasomodulators under normal and stress conditions.
  
  
  METHODS
  Cells were cultured for 24 h and treated with H2O2 (25 microM) for 6 h and subsequently with endothelin-1 (10 nM) for 10 min. Eicosanoid release was assessed in the media by enzyme immunoassay.
  
  
  RESULTS
  Endothelin-1 mediated cPLA2 phosphorylation and increased prostaglandin (PG) I2, PGE2 and thromboxane A2 (TXA2) release in endothelial cells while it only increased TXA2 in Kupffer cells. H2O2 significantly increased PGI2, PGE2 and TXA2 in endothelial cells through an upregulation of cyclooxygenase-2, thromboxane synthase A2, and phosphorylation of cPLA2. Endothelin-1-induced PGI2, PGE2, and TXA2 release in endothelial cells were inhibited by H2O2 correlating with the absence of further cPLA2 phosphorylation. In Kupffer cells, H2O2 only increased TXA2 synthesis and further endothelin-1 stimulation of TXA2 was possible through a higher increase in cPLA2.
  
  
  CONCLUSIONS
  These results indicate that under normal conditions endothelial cells play a pivotal role in liver microcirculation regulation. Oxidative stress not only disrupts the basal balance of vasomodulators in the liver but also affects endothelin-1-induced effects in both Kupffer cells and endothelial cells.
authors.affiliation: Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
authors.forename: Amel
authors.initials: A
authors.lastname: Karaa
authors.forename: Walid S
authors.initials: WS
authors.lastname: Kamoun
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Jain
authors.initials: J
authors.lastname: Zhang
authors.forename: Mark G
authors.initials: MG
authors.lastname: Clemens
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010741:Phospholipases A / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015777:Eicosanoids; D019332:Endothelin-1; D016877:Oxidants; D006861:Hydrogen Peroxide; D010741:Phospholipases A