Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis-element in cardiac myocytes.

摘要: We described recently the activation of Janus kinasesignal transducer and activator transcription (JakSTAT) mitogen-activated protein (MAP) kinase pathways by leukemia inhibitory factor (LIF) through gp130, a signal IL-6-related cytokines, that transduces hypertrophic signals in cardiac myocytes. In addition, stimulation gp130 cytokines is known to exert cytoprotective effect. present study, we investigated possibility initiates genes Incubation myocytes with LIF induced expression bcl-x, isoform was identified as bcl-xL. Induction bcl-xL also Western blotting. Antisense oligonucleotide against bcl-x mRNA inhibited protective effect accompanied reduction bclxL protein. constructed promoter-luciferase reporter gene plasmids (-639/+10- or -161/+10-luciferase), transfected them increased luciferase activity -639/+10-luciferase plasmids. Although -161/+10-luciferase presented comparable responsiveness LIF, basal level impaired. The LIF-responsive cis-element localized DNA fragment (positions -161 +10) contains an interferon-gamma site (GAS) motif (GGA) at position -41 promoter. This bound STAT1, not STAT3, site-directed mutagenesis revealed this essential for promoter activity. These data suggest induces via STAT1 binding myocytes, presenting