TY - JOUR
T1 - Regulation of rat cardiac myocyte growth by a neuronal factor secreted by PC12 cells
AU - Atkins, Dianne L.
AU - Krumm, Penny A.
AU - Schutte, Brian C.
AU - Harrison, Jeffrey D.
AU - Green, Steven H.
PY - 1997/6
Y1 - 1997/6
N2 - Sympathetic innervation of cardiac myocytes in vitro induces growth independent of anatomic contact between the neurons and myocytes and is not mediated by α- or β-adrenergic receptor stimulation. To establish a model system that will allow purification and identification of the neuronal factor(s) responsible for mediating this regulation, we have initiated studies utilizing conditioned medium from the PC12 cell line. PC12 cells acquire a cholinergic sympathetic neuronal phenotype when exposed to nerve growth factor. Culture medium conditioned by neuronal PC12 cells, but not nonneuronal PC12 cells, induces growth in newborn rat cardiac myocytes as measured by surface area and [35S]methionine incorporation into protein and increases expression of atrionatriuretic peptide, a marker for myocyte hypertrophy. The magnitude of the growth response is dose-dependent and mimics the response to sympathetic innervation. The myocyte response to conditioned medium is not detectable after 24 h of exposure; maximal rate of protein synthesis is obtained within 48 h. Neuronally differentiated PC12 cell-conditioned medium stimulation of growth could not be mimicked by α- or β-adrenergic agonists or muscarinic agonists, nor inhibited by α- or β- adrenergic antagonists, nor by muscarinic antagonists. Neuropeptide Y and somatostatin, peptides known to be present in PC12 cells and sympathetic neurons, were also ineffective at reproducing the effect of neuronally differentiated PC12 cell conditioned medium. These data indicate that neuronal cells release a soluble factor, different from neurotransmitter, which stimulates myocyte growth. They further identify the PC12 cell line as providing a convenient and abundant supply of this molecule, thus facilitating its further characterization.
AB - Sympathetic innervation of cardiac myocytes in vitro induces growth independent of anatomic contact between the neurons and myocytes and is not mediated by α- or β-adrenergic receptor stimulation. To establish a model system that will allow purification and identification of the neuronal factor(s) responsible for mediating this regulation, we have initiated studies utilizing conditioned medium from the PC12 cell line. PC12 cells acquire a cholinergic sympathetic neuronal phenotype when exposed to nerve growth factor. Culture medium conditioned by neuronal PC12 cells, but not nonneuronal PC12 cells, induces growth in newborn rat cardiac myocytes as measured by surface area and [35S]methionine incorporation into protein and increases expression of atrionatriuretic peptide, a marker for myocyte hypertrophy. The magnitude of the growth response is dose-dependent and mimics the response to sympathetic innervation. The myocyte response to conditioned medium is not detectable after 24 h of exposure; maximal rate of protein synthesis is obtained within 48 h. Neuronally differentiated PC12 cell-conditioned medium stimulation of growth could not be mimicked by α- or β-adrenergic agonists or muscarinic agonists, nor inhibited by α- or β- adrenergic antagonists, nor by muscarinic antagonists. Neuropeptide Y and somatostatin, peptides known to be present in PC12 cells and sympathetic neurons, were also ineffective at reproducing the effect of neuronally differentiated PC12 cell conditioned medium. These data indicate that neuronal cells release a soluble factor, different from neurotransmitter, which stimulates myocyte growth. They further identify the PC12 cell line as providing a convenient and abundant supply of this molecule, thus facilitating its further characterization.
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U2 - 10.1203/00006450-199706000-00007
DO - 10.1203/00006450-199706000-00007
M3 - Article
C2 - 9167196
AN - SCOPUS:0030979260
SN - 0031-3998
VL - 41
SP - 832
EP - 841
JO - Pediatric Research
JF - Pediatric Research
IS - 6
ER -