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Troglitazone inhibits endothelial cell proliferation through suppression of casein kinase 2 activity

Kuy-Sook Lee1, Jin-Hee Park, Seahyoung Lee

  • 1Center for Biological Sciences, Division of Cardiovascular Diseases, National Institute of Health, Seoul, Republic of Korea.

Biochemical and Biophysical Research Communications
|June 9, 2006
PubMed

Insights

Troglitazone inhibits endothelial cell proliferation by decreasing casein kinase 2 (CK2) activity. This allows phosphatase and tensin homolog deleted from chromosome 10 (PTEN) to remain active, suppressing Akt signaling independently of PPARgamma.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Troglitazone, a PPARgamma agonist, inhibits endothelial cell proliferation via Akt suppression.
  • PTEN's role in troglitazone's effect is proposed but mechanistically unclear.
  • CK2 negatively regulates PTEN activity, suggesting a potential link.

Purpose of the Study:

  • To investigate the effect of troglitazone on CK2 activity.
  • To elucidate the mechanism by which troglitazone regulates PTEN.
  • To determine if troglitazone's effect on HUVECs is PPARgamma-dependent.

Main Methods:

  • Human Umbilical Vein Endothelial Cells (HUVECs) were treated with troglitazone.
  • Cell proliferation, Akt activation, and PTEN phosphorylation were assessed.
  • Casein kinase 2 (CK2) activity was measured.
  • The effect of a CK2 inhibitor (DRB) was evaluated.

Main Results:

  • Troglitazone inhibited serum-induced HUVEC proliferation concentration-dependently.
  • Troglitazone attenuated serum-induced Akt activation and downstream signaling.
  • Troglitazone decreased PTEN phosphorylation, inversely correlating with CK2 activity.
  • CK2 inhibition mimicked troglitazone's effects on Akt and downstream pathways.

Conclusions:

  • Troglitazone inhibits HUVEC proliferation by suppressing CK2 activity.
  • This suppression leads to sustained PTEN activation, inhibiting Akt signaling.
  • The observed effects appear independent of PPARgamma activation.

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