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

Mol Cell Endocrinol. 2009 Feb 27;299(2):232-9. doi: 10.1016/j.mce.2008.12.006. Epub 2008 Dec 24.

Abstract

The ghrelin receptor (GHS-R1a) displays a high level of constitutive signaling through a phospholipase C/protein kinase C-dependent pathway. Therefore, we have investigated the role of agonist-dependent and agonist-independent signaling of GHS-R1a in apoptosis using the seabream GHS-R1a stably expressed in human embryonic kidney 293 cells (HEK-sbGHS-R1a cells). Cadmium-induced activation of caspase-3 was significantly attenuated in HEK-sbGHS-R1a cells compared to wild-type HEK293 cells, while the apoptotic responses to the protein kinase C inhibitor staurosporine were similar. GHS-R1a ligands had no effect on caspase-3 activation or on cell proliferation. Concentrations of the inverse agonist [d-Arg(1),d-Phe(5),d-Trp(7,9),Leu(11)]-substance P sufficient to inhibit constitutive inositol phosphate generation did not enhance caspase-3 activity, suggesting a possible role of phosphatidylcholine-specific phospholipase C in the anti-apoptotic activity of GHS-R1a. In conclusion, our data suggests that the constitutive activity of sbGHS-R1a may be sufficient alone to attenuate apoptosis via a protein kinase C-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects
  • Enzyme Activation / drug effects
  • Humans
  • Oligopeptides / pharmacology
  • Protein Kinase C / metabolism*
  • Receptors, Ghrelin / agonists
  • Receptors, Ghrelin / antagonists & inhibitors
  • Receptors, Ghrelin / metabolism*
  • Sea Bream / metabolism*
  • Staurosporine / pharmacology
  • Transfection
  • Type C Phospholipases / metabolism

Substances

  • GHRP-6, Lys(3)-
  • Oligopeptides
  • Receptors, Ghrelin
  • Protein Kinase C
  • Type C Phospholipases
  • Caspase 3
  • Staurosporine