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Differential Effects of Oxidative Stress on Hepatic Endothelial and Kupffer Cell Eicosanoid Release in Response to Endothelin‐1
Author(s) -
KARAA AMEL,
KAMOUN WALID S.,
XU HONG,
ZHANG JAIN,
CLEMENS MARK G.
Publication year - 2006
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680600776278
Subject(s) - endocrinology , endothelin 1 , medicine , eicosanoid , endothelin receptor , endothelial stem cell , thromboxane b2 , thromboxane , prostaglandin , nitric oxide , thromboxane a2 , chemistry , endothelins , biology , biochemistry , arachidonic acid , in vitro , platelet , enzyme , receptor
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 H 2 O 2 (25 μM) 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 cPLA 2 phosphorylation and increased prostaglandin (PG) I 2 , PGE 2 and thromboxane A 2 (TXA 2 ) release in endothelial cells while it only increased TXA 2 in Kupffer cells. H 2 O 2 significantly increased PGI 2 , PGE 2 and TXA 2 in endothelial cells through an upregulation of cyclooxygenase‐2, thromboxane synthase A 2 , and phosphorylation of cPLA 2 . Endothelin‐1‐induced PGI 2 , PGE 2 , and TXA 2 release in endothelial cells were inhibited by H 2 O 2 correlating with the absence of further cPLA 2 phosphorylation. In Kupffer cells, H 2 O 2 only increased TXA 2 synthesis and further endothelin‐1 stimulation of TXA 2 was possible through a higher increase in cPLA 2 . Conclusion: 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.