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Stimulation of the ICAM-1 gene transcription by the peroxovanadium compound [bpV(Pic)] involves STAT-1 but not

M Audette1, L Larouche, I Lussier

  • 1Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL) and Laval University, Québec, Canada.maudette@drschul.ulaval.ca

European Journal of Biochemistry
|March 15, 2001
PubMed

Insights

Peroxovanadium compounds activate intercellular adhesion molecule-1 (ICAM-1) gene transcription by targeting the interferon-gamma-responsive element. This suggests a role in regulating the JAK/STAT pathway via protein tyrosine phosphatase inhibition.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Vanadate and peroxovanadium compounds inhibit protein tyrosine phosphatases (PTPs) and mimic insulin action.
  • Intercellular adhesion molecule-1 (ICAM-1) plays a role in cellular adhesion and immune responses.

Purpose of the Study:

  • To investigate the mechanism by which bpV(Pic), a peroxovanadium derivative, activates ICAM-1 gene transcription.
  • To identify the specific DNA elements and signaling pathways involved in bpV(Pic)-mediated ICAM-1 induction.

Main Methods:

  • Utilized deletion and site-specific mutants of the ICAM-1 promoter linked to a luciferase reporter gene in 293 and 293T cells.
  • Performed transient transfections and electrophoretic mobility-shift assays (EMSA).
  • Assessed synergistic effects with interferon-gamma.

Main Results:

  • bpV(Pic) activated ICAM-1 transcription, primarily through the palindromic interferon-gamma-responsive element (pI gamma RE)/gamma-interferon activated sequence (GAS) site.
  • Mutation of the NF-kappa B site did not affect bpV(Pic) responsiveness.
  • bpV(Pic) enhanced interferon-gamma's effect on ICAM-1 promoter activity and induced signal transducers and activators of transcription (STAT)-1 binding.

Conclusions:

  • The peroxovanadium compound bpV(Pic) activates ICAM-1 transcription via the pI gamma RE/GAS site.
  • bpV(Pic) likely inhibits PTPs involved in the JAK/STAT signaling pathway, leading to STAT-1 activation and ICAM-1 induction.

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