The constitutive activity of the ghrelin receptor attenuates apoptosis via a protein kinase C-dependent pathway.
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.
Lau
Pui Ngan
PN
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Chow
Kevin B S
KB
Chan
Chi-Bun
CB
Cheng
Christopher H K
CH
Wise
Helen
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021541:Sea Bream / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
C520836:GHRP-6, Lys(3)-; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D053148:Caspase 3; D019311:Staurosporine