© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes
aUnidad de Investigación del Servicio de Cardiología, Laboratorio de Investigación 1, Planta Baja, Area de Investigación y Docencia, Hospital Clínico Universitario de Santiago de Compostela, Travesía Choupana s/n, 15706, Santiago de Compostela, Spain
bDepartamento de Ciencias Morfológicas, Universidad de Santiago de Compostela, Spain
cDepartamento de Fisiología, Universidad de Santiago de Compostela, Spain
dUnidad de Investigación del Servicio de Reumatología, Laboratorio de Investigación 4, Hospital Clínico Universitario, Santiago de Compostela, Spain
* Corresponding author. Tel.: +34-981-950902; fax: +34-981-951068. Email address: frlago{at}usc.es
Objective: Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of growth hormone (GH) and promotes appetite and adiposity. It has also been reported to increase myocardial contractility, induce vasodilation, and protect against myocardial-infarction-induced heart failure. Though principally gastric in origin, it is also produced by other tissues. This work investigated whether cardiomyocytes synthesize and secrete ghrelin, and how its production in these cells responds to stress and exogenous apoptotic agents. Methods: Ghrelin and its receptor expression was studied by RT-PCR, immunohistochemistry, and competitive binding studies in mouse adult cardiomyocyte cell line HL-1, and primary cultured human cardiomyocytes. Ghrelin accumulation in cardiomyocyte culture medium was measured by radioimmunoassay. Viability and apoptosis assays were carried on by MTT and Hoechst dye vital staining, respectively. Results: RT-PCR showed that HL-1 cells produce mRNAs for both ghrelin and GHS-R, and that GHS-R1a is expressed in human cardiomyocytes; and competitive binding studies using 125I-labelled ghrelin showed efficient constitutive expression of GHS-R at the surface of HL-1 cells. Immunohistochemistry confirmed the presence of ghrelin in the cytoplasm of HL-1 cells and of isolated human cardiomyocytes in primary culture. Radioimmunoassay showed that ghrelin was secreted by HL-1 cells and human cardiomyocytes into the culture medium. Ghrelin did not modify the viability of HL-1 cells subjected to 12-h starvation, but did protect against the apoptosis inducer cytosine arabinoside (AraC). Finally, production of ghrelin mRNA in HL-1 cardiomyocytes was reduced by AraC but increased if exposure to AraC was preceded by GH treatment. Conclusions: Ghrelin is synthesized and secreted by isolated murine and human cardiomyocytes, probably with paracrine/autocrine effects, and may be involved in protecting these cells from apoptosis.
KEYWORDS Apoptosis; Cell culture/isolation; Growth factors; Hormones; Cardiomyocytes; Receptors
Time for primary review 15 days
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