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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

The constitutive activity of the ghrelin receptor attenuates apoptosis via a protein kinase C-dependent pathway

Pui Ngan Lau1, Kevin B S Chow, Chi-Bun Chan

  • 1Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.

Molecular and Cellular Endocrinology
|January 13, 2009
PubMed

Insights

The ghrelin receptor (GHS-R1a) constitutively signals, reducing apoptosis via protein kinase C. This intrinsic activity, independent of external ligands, protects cells from programmed cell death.

Area of Science:

  • Cell Biology
  • Molecular Endocrinology
  • Apoptosis Research

Background:

  • The ghrelin receptor (GHS-R1a) exhibits significant constitutive signaling.
  • This signaling pathway involves phospholipase C and protein kinase C.
  • Understanding GHS-R1a's role in apoptosis requires investigating both agonist-dependent and independent signaling.

Purpose of the Study:

  • To investigate the role of constitutive and ligand-dependent signaling of seabream GHS-R1a (sbGHS-R1a) in apoptosis.
  • To determine if sbGHS-R1a activity influences caspase-3 activation and cell proliferation.
  • To elucidate the specific pathways involved in sbGHS-R1a's potential anti-apoptotic effects.

Main Methods:

  • Stable expression of seabream GHS-R1a in human embryonic kidney 293 cells (HEK-sbGHS-R1a).
  • Induction of apoptosis using cadmium and the protein kinase C inhibitor staurosporine.
  • Measurement of caspase-3 activation and cell proliferation.
  • Assessment of signaling with an inverse agonist targeting inositol phosphate generation.

Main Results:

  • Cadmium-induced caspase-3 activation was significantly reduced in HEK-sbGHS-R1a cells compared to wild-type cells.
  • Apoptotic responses to staurosporine were similar in both cell types.
  • GHS-R1a ligands did not affect caspase-3 activation or cell proliferation.
  • An inverse agonist inhibiting constitutive inositol phosphate generation did not increase caspase-3 activity.

Conclusions:

  • The constitutive activity of sbGHS-R1a is sufficient to attenuate apoptosis.
  • This anti-apoptotic effect is mediated through a protein kinase C-dependent pathway.
  • Phosphatidylcholine-specific phospholipase C may play a role in the anti-apoptotic function of GHS-R1a.

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