Regulation of rat cardiac myocyte growth by a neuronal factor secreted by PC12 cells
Abstract
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 inhibite...Continue Reading
References
Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines
Citations
Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics.
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