Neuropeptide Y stimulates hypertrophy of adult ventricular cardiomyocytes.
It was investigated whether neuropeptide Y (NPY) could exert a trophic effect on ventricular myocytes isolated from the adult rat heart. Two different culture models were used: day 1 and 7 cultures of cardiomyocytes. In day 1 and 7 cultures, NPY caused an increase in cellular protein mass. In day 1 cultures, NPY (10 nM) increased the protein-to-DNA ratio within 24 h by 10.1 +/- 2.8% (P < 0.01), but did not stimulate the incorporation of [14C]phenylalanine into cell proteins. The degradation of proteins was retarded in presence of NPY, revealed by pulse-chase experiments. In day 7 cultures, NPY (10 nM) increased the protein-to-DNA ratio within 24 h by 33.9 +/- 5.0% (P < 0.01), increased the RNA-to-DNA ratio by 19.2 +/- 6.4%, and stimulated the incorporation of [14C]phenylalanine by 45.5 +/- 4.5% (P < 0.01). As in day 1 cultures, protein degradation was retarded. The specific activities of cytosolic creatine kinase and lactate dehydrogenase were increased in presence of NPY. This study demonstrates for the first time that NPY is a trophic factor for cardiomyocytes. NPY can cause an increase in cellular mass of protein, i.e., hypertrophy, by two mechanisms: 1) reduction of degradation of protein, found in day 1 and 7 cultures, and 2) stimulation of protein synthesis, observed only in day 7 cultures. The responsiveness of protein synthesis to NPY stimulation is induced during prolonged incubation in culture.
Millar
B C
BC
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Schlüter
K D
KD
Zhou
X J
XJ
McDermott
B J
BJ
Piper
H M
HM
D000818:Animals; D006332:Cardiomegaly / Q000473:pathology*; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009478:Neuropeptide Y; D011506:Proteins; D004247:DNA; D008715:Methionine; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase