Liang J F, Akaike T
National Key Laboratory of Biomembrane and Membrane Engineering, School of Life Science and Engineering, Tsinghua University, Beijing, People's Republic of China.
Biochem Biophys Res Commun. 1998 Feb 24;243(3):833-7. doi: 10.1006/bbrc.1998.8190.
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.
肝细胞有丝分裂原（HGF和EGF）可抑制脂多糖与细胞因子混合物（称为LPS/CM）诱导的肝细胞中一氧化氮（NO）合成及细胞损伤。有丝分裂抑制剂如羟基脲和渥曼青霉素无法逆转EGF或HGF对NO生成的抑制作用，而它们二者对肝细胞NO合成均有一定抑制作用。虽然佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）激活蛋白激酶C（PKC）对肝细胞NO合成无影响，但长期用PMA处理肝细胞使PKC活性缺失后，可消除LPS/CM诱导的NO生成。此外，用HGF和EGF预处理肝细胞也可阻断LPS/CM诱导的肝细胞NO合成。这些结果表明，增殖信号并非直接参与肝细胞中有丝分裂原抑制的NO合成，且LPS/CM介导的NO合成与肝细胞的代谢/氧化还原状态相关。
