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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+-dependent apoptotic stimuli

Saverio Marchi1, Alessandro Rimessi, Carlotta Giorgi

  • 1Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Via Borsari 46, I-44100 Ferrara, Italy.

Biochemical and Biophysical Research Communications
|August 30, 2008
PubMed

Insights

The proto-oncogene Akt inhibits apoptosis by reducing calcium release from the endoplasmic reticulum. This impacts cellular calcium responses and decreases sensitivity to proapoptotic stimuli, revealing Akt's role in calcium homeostasis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • The proto-oncogene Akt is a key apoptosis inhibitor, frequently activated in human cancers.
  • Inositol 1,4,5-trisphosphate receptors (IP3Rs) mediate calcium (Ca2+) transfer from the endoplasmic reticulum (ER) to mitochondria during apoptosis.
  • Akt phosphorylates IP3R, suggesting a regulatory role in calcium signaling.

Purpose of the Study:

  • To investigate the effect of activated Akt on intracellular calcium (Ca2+) release and homeostasis.
  • To determine if Akt-mediated alterations in Ca2+ signaling affect cellular sensitivity to apoptosis.

Main Methods:

  • Overexpression of constitutively active myristoylated/palmitylated AKT1 (m/p-AKT1) in HeLa cells.
  • Measurement of Ca2+ release from the ER upon agonist stimulation.
  • Assessment of cytosolic and mitochondrial Ca2+ responses.
  • Evaluation of cellular sensitivity to Ca2+-mediated proapoptotic stimuli.

Main Results:

  • HeLa cells overexpressing m/p-AKT1 exhibited reduced Ca2+ release from the ER.
  • This reduction affected both cytosolic and mitochondrial Ca2+ dynamics following ER Ca2+ release.
  • Cells with altered ER Ca2+ content showed significantly decreased sensitivity to proapoptotic stimuli mediated by Ca2+.

Conclusions:

  • Activated Akt plays a crucial role in regulating intracellular Ca2+ homeostasis.
  • Akt's modulation of ER Ca2+ release contributes to its anti-apoptotic function.
  • Targeting Akt may offer therapeutic strategies for cancer by influencing Ca2+-dependent cell death pathways.

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