Endothelin-1 induces glut1 transcription through enhanced interaction between Sp1 and NF-kappaB transcription factors.

We have shown previously that endothelin-1 (ET-1) induction of Glut1 transcription is mediated by ET-1 responsive elements on enhancer 2, via both protein kinase Cepsilon (PKCepsilon)- and p42/p44 mitogen-activated protein kinase (MAPK)-dependent pathways. In the present study, we further explored the molecular mechanism involved. By using mutation constructs of luciferase ...
reporter driven by Glut1 promoter/enhancers, chromatin immunoprecipitation and co-immunoprecipitation experiments, we were able to demonstrate that cooperative interaction between NF-kappaB and Sp1 were required to enhance Glut1 transcription in response to ET-1. While ET-1 may induce Sp1 expression via both PKC-and MAPK-dependent pathways, activation of NF-kappaB by ET-1 is mediated by a PKCepsilon/reactive oxygen species (ROS) cascade. Taken together, these results suggest that by activating NF-kappaB via PKCepsilon/ROS cascade and increasing Sp1 expression through both PKCepsilon- and MAPK-dependent pathways, ET-1 may activate Glut1 transcription by enhancing interaction between nuclear NF-kappaB and Sp1 as well as their binding to enhancer 2.
Mesh Terms:
3T3-L1 Cells, Adipocytes, Animals, Cell Nucleus, Chromatin Immunoprecipitation, Cyclic AMP Response Element-Binding Protein, Endothelin-1, Genes, Reporter, Glucose Transporter Type 1, Luciferases, Mice, Mitogen-Activated Protein Kinases, Mutagenesis, Site-Directed, NF-kappa B, Promoter Regions, Genetic, Protein Binding, Protein Kinase C-epsilon, RNA, Messenger, Reactive Oxygen Species, Signal Transduction, Sp1 Transcription Factor, Transcription Factor RelA, Transcription, Genetic, Transfection, Up-Regulation
Cell. Signal.
Date: Apr. 01, 2008
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