Evidence that AMP-activated protein kinase can negatively modulate ornithine decarboxylase activity in cardiac

Catherine L Passariello1, Davide Gottardi, Silvia Cetrullo

  • 1Department of Biochemistry, University of Bologna, Bologna, Italy.

Insights

Isoproterenol activates both cell growth (ODC) and energy sensing (AMPK) in heart cells. AMPK activation negatively regulates ODC activity, suggesting a mechanism to control cell growth.

Area of Science:

  • Molecular Cardiology
  • Cellular Metabolism
  • Biochemistry

Background:

  • AMP-activated protein kinase (AMPK) links energy status to cell growth.
  • Ornithine decarboxylase (ODC) is crucial for polyamine biosynthesis and cell growth, implicated in cardiac hypertrophy.
  • Isoproterenol is a known stimulator of cardiac cells.

Purpose of the Study:

  • To investigate the interplay between AMPK and ODC responses to isoproterenol in H9c2 cardiomyoblasts.
  • To elucidate the role of AMPK in regulating ODC activity and cell growth.

Main Methods:

  • Treatment of H9c2 cardiomyoblasts and SH-SY5Y neuroblastoma cells with isoproterenol.
  • Measurement of ODC activity and protein synthesis.
  • Assessment of AMPK phosphorylation and activity using siRNA and shRNA for AMPK subunit knockdown.

Main Results:

  • Isoproterenol rapidly induced ODC activity, dependent on the PI3K/Akt pathway.
  • Isoproterenol stimulated AMPK phosphorylation (Thr172) and ACC phosphorylation (Ser72).
  • AMPK knockdown led to ODC superinduction, even in the absence of isoproterenol, indicating a negative regulatory role.

Conclusions:

  • Isoproterenol activates opposing pathways: ODC for growth and AMPK for energy homeostasis.
  • AMPK activation negatively modulates ODC activity, providing a mechanism to control cell growth.
  • This AMPK-mediated regulation of ODC may be a key factor in managing cardiac cell growth and hypertrophy.

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