Inhibition of Apolipoprotein A-I Expression by TNF-Alpha in HepG2 Cells: Requirement for c-jun

摘要: Tumor necrosis factor alpha (TNF α) signals in part through the mitogen activated protein (MAP) kinase c-jun-N-terminal (JNK). Activation of JNK has been shown to promote insulin resistance and dyslipidemia, including reductions plasma high-density lipoprotein (HDL) apolipoprotein A-I (apo A-I). To examine how TNF α-mediated activation inhibits hepatic apo production, effects c-jun on gene expression were examined HepG2 cells. Apo promoter activity measured by Northern Western blotting transient transfection. Transient transfection siRNA used specifically over-express or knockout c-jun, kinase-1 -2 (JNK1 JNK2, respectively) mitogen-activated kinase-4 (MKK4). α-treatment cells induced rapid phosphorylation serine 63. In treated with phorbol-12-myristate-13-acetate (PMA), was inhibited mRNA content secretion decreased. Likewise, over-expression JNK1 JNK2 activity. Over-expression constitutively active MKK4, an upstream that directly activates JNK, also activity, while a dominant-negative MKK4 de-repressed α-treated Inhibition synthesis using but not control prevented inhibition A-I. These results suggest MKK4/JNK/c-jun signaling pathway mediates α-dependent synthesis. J. Cell. Biochem. 115: 253–260, 2014. © 2013 Wiley Periodicals, Inc.