Open AccessStimulation of the ICAM‐1 gene transcription by the peroxovanadium compound [bpV(Pic)] involves STAT‐1 but not NF‐κB activation in 293 cells
Author(s) -
Audette Marie,
Larouche Lucie,
Lussier Isabelle,
Fugère Nathalie
Publication year - 2001
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.2001.02054.x
Subject(s) - stat , stimulation , microbiology and biotechnology , chemistry , nf κb , nfkb1 , transcription factor , signal transduction , cancer research , gene , biology , biochemistry , endocrinology , stat3
Vanadate and peroxovanadium derivatives are potent inhibitors of protein tyrosine phosphatases (PTPs) and exhibit insulinomimetic activities in several cell systems. We have found that in 293 and 293T cells, intercellular adhesion molecule‐1 (ICAM‐1) gene transcription is activated by bpV(Pic), a picolinic acid‐stabilized peroxovanadium derivative. To identify the bpV(Pic)‐responsive element(s), several deletion and site‐specific mutants of the ICAM‐1 gene promoter cloned upstream from the firefly luciferase reporter gene were transiently transfected into both cell lines. Deletion or site‐specific mutation of the NF‐κB site did not affect bpV(Pic) responsiveness, whereas deletion or mutation of the palindromic interferon‐γ‐responsive element (pIγRE)/γ‐interferon activated sequence site greatly decreased bpV(Pic) responsiveness in both cell types. bpV(Pic) synergistically co‐operated with interferon‐γ to increase the transcriptional activity of the ICAM‐1 promoter. Electrophoretic mobility‐shift assays showed that bpV(Pic) induces signal transducers and activators of transcription (STAT)‐1 binding to the ICAM‐1 pIγRE/GAS in 293T cells, suggesting that the peroxovanadium compound specifically inhibits the phosphatase(s) required to regulate the JAK/STAT signal‐transduction pathway.