Document Detail

Regulation of rat cardiac myocyte growth by a neuronal factor secreted by PC12 cells.
MedLine Citation:
PMID:  9167196     Owner:  NLM     Status:  MEDLINE    
Sympathetic innervation of cardiac myocytes in vitro induces growth independent of anatomic contact between the neurons and myocytes and is not mediated by alpha- or beta-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 alpha- or beta-adrenergic agonists or muscarinic agonists, nor inhibited by alpha- or beta-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.
D L Atkins; P A Krumm; B C Schutte; J D Harrison; S H Green
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pediatric research     Volume:  41     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-07-18     Completed Date:  1997-07-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  832-41     Citation Subset:  IM    
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
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MeSH Terms
Animals, Newborn
Atrial Natriuretic Factor / biosynthesis
Biological Factors / pharmacology,  secretion*
Cell Division / drug effects
Cells, Cultured
Culture Media, Conditioned
Methionine / metabolism
Myocardium / cytology*,  metabolism
PC12 Cells / physiology*
Polymerase Chain Reaction
Protein Biosynthesis
Rats, Inbred WKY
Grant Support
Reg. No./Substance:
0/Biological Factors; 0/Culture Media, Conditioned; 63-68-3/Methionine; 85637-73-6/Atrial Natriuretic Factor

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