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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

Signalling of the M3-muscarinic receptor to the anti-apoptotic pathway

David C Budd1, Elizabeth J Spragg, Katie Ridd

  • 1Department of Cell Physiology and Pharmacology, University of Leicester, P.O. Box 138, University Road, Leicester LE1 9HN, UK.

The Biochemical Journal
|April 8, 2004
PubMed

Insights

The M3-muscarinic receptor prevents programmed cell death (apoptosis) by up-regulating Bcl-2 protein. This anti-apoptotic effect involves gene transcription but not calcium signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Programmed cell death (apoptosis) is crucial for tissue homeostasis and development.
  • G-protein-coupled receptors are key regulators of apoptosis.
  • The M3-muscarinic receptor's role in apoptosis requires further elucidation.

Purpose of the Study:

  • To investigate the anti-apoptotic signaling mechanism of the Gq/11-coupled M3-muscarinic receptor.
  • To determine the involvement of calcium/phospholipase C signaling in this process.
  • To explore the role of gene transcription and Bcl-2 protein in M3-muscarinic receptor-mediated apoptosis regulation.

Main Methods:

  • Utilized a Chinese hamster ovary (CHO) cell model.
  • Assessed M3-muscarinic receptor's effect on apoptosis induced by etoposide.
  • Investigated the impact of actinomycin D on M3-muscarinic receptor signaling.
  • Measured Bcl-2 protein levels.

Main Results:

  • M3-muscarinic receptor activation conferred an anti-apoptotic effect independent of calcium/phospholipase C.
  • This response was sensitive to actinomycin D, indicating a role for gene transcription.
  • M3-muscarinic receptor stimulation attenuated the etoposide-induced decrease in anti-apoptotic Bcl-2 protein.

Conclusions:

  • The M3-muscarinic receptor signals to anti-apoptotic pathways through a mechanism involving gene transcription.
  • This signaling pathway up-regulates Bcl-2 protein levels, counteracting apoptosis.
  • The anti-apoptotic function of M3-muscarinic receptors is distinct from calcium/phospholipase C signaling pathways.

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