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PTH inactivates the AKT survival pathway in the colonic cell line Caco-2

Natalia Calvo1, Ana Russo de Boland, Claudia Gentili

  • 1Department Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, (8000) Bahía Blanca, Argentina.

Biochimica Et Biophysica Acta
|December 17, 2009
PubMed

Insights

Parathyroid hormone (PTH) triggers intestinal cell apoptosis by inactivating the AKT survival pathway. This involves the phosphatase PP2A and the cAMP pathway, leading to Caco-2 cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Previous studies established that parathyroid hormone (PTH) induces apoptosis in human Caco-2 intestinal cells via the mitochondrial pathway.
  • The AKT signaling pathway is crucial for cell survival, and its modulation by PTH in intestinal cells warrants investigation.

Purpose of the Study:

  • To investigate the role of the AKT survival pathway in PTH-induced intestinal cell apoptosis.
  • To elucidate the specific mechanisms by which PTH modulates AKT activity and its downstream effectors in Caco-2 cells.

Main Methods:

  • Investigated the interaction and activity of AKT and protein phosphatase 2A (PP2A) in response to PTH.
  • Utilized cell fractionation to track the subcellular localization of PP2A catalytic subunit (PP2Ac).
  • Assessed the involvement of cAMP, protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK) pathways.

Main Results:

  • PTH treatment leads to AKT dephosphorylation, mediated by PP2A, and promotes PP2Ac association with AKT and its translocation to mitochondria.
  • PP2A activity is essential for PTH-induced Caco-2 cell viability and the activation of caspase-3 and PARP cleavage.
  • The cAMP pathway contributes to PTH-induced AKT dephosphorylation, whereas PKC and p38 MAPK are not involved.

Conclusions:

  • PP2A and the cAMP pathway cooperate to inhibit the AKT survival pathway, promoting PTH-induced apoptosis in Caco-2 intestinal cells.
  • PTH modulates the interaction of AKT with 14-3-3 proteins, potentially influencing cell survival signaling.
  • These findings reveal novel mechanisms underlying PTH's effects on intestinal cell fate.

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