Mitogenic-factor-dependent regulation of lipopolysaccharide and cytokine mixture-mediated hepatocyte nitric oxide synthesis in vitro.
Hepatocellular mitogen (HGF and EGF) inhibited lipopolysaccharide and cytokine mixture (referred as LPS/CM)-induced NO synthesis and cellular injury in hepatocytes. Mitogenic inhibitors such as hydroxyurea and Wortmannin could not reverse EGF or HGF-inhibited NO production, whereas both of them showed some inhibitory effect on hepatocyte NO synthesis. Although activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) had no effect on hepatocyte NO synthesis, deletion of PKC activity by long-term treatment of hepatocytes with PMA abolished LPS/CM-induced NO production. In addition, pretreatment of hepatocytes with HGF and EGF also blocked LPS/CM-induced NO synthesis in the hepatocyte. These results suggest that proliferating signal is not directly involved in mitogen-inhibited NO synthesis in the hepatocyte, and LPS/CM-mediated NO synthesis is associated with the metabolic/redox state of hepatocytes.
Liang
J F
JF
National Key Laboratory of Biomembrane and Membrane Engineering, School of Life Science and Engineering, Tsinghua University, Beijing, People's Republic of China.
Akaike
T
T
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008934:Mitogens / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D016207:Cytokines; D008070:Lipopolysaccharides; D008934:Mitogens; D009569:Nitric Oxide; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D006918:Hydroxyurea; D000077191:Wortmannin