title: Combinatorial code of growth factors and neuropeptides define neuroendocrine differentiation in PC12 cells.
abstract: Adrenal chromaffin cells constitute one of the first cell types to have been defined as a neuroendocrine cell type. Since they produce dopamine, these cells have been proposed for the treatment of neuronal deficits in human Parkinson's disease. However, the factors involved in the development of chromaffin cells are still poorly understood. Based on recent insights from stem cell research, we decided to study the role of extracellular matrices, growth factors and neuropeptides on the neuroendocrine differentiation in a serum-free medium of PC12 cells. Employing immunohistochemistry, quantitative PCR and HPLC analysis, neuroendocrine differentiation was determined by evaluating neurite outgrowth, catecholamine biosynthesis and release as well as neuropeptide and vesicular protein mRNA expression. The combination of bFGF, NGF and PACAP could prevent the inhibition of neurite process development induced by dexamethasone in PC12 cells cultured on ECM. Whereas glucocorticoids were essential in the regulation of enzymes of catecholamine biosynthesis and metabolism, growth factors and PACAP were more efficient in inducing neuropeptide and chromogranin B expression as well as release of dopamine and 3-methoxytyramine. Therefore, in addition to glucocorticoids, chromaffin cells need a gradient of matrix, growth factors, and neuropeptides to develop the full functional phenotype of a neuroendocrine cell.
authors.affiliation: Department of Endocrinology, University of Düsseldorf, 40225, Düsseldorf, Germany. delphine.beaujean@univ-rouen.fr
authors.forename: Delphine
authors.initials: D
authors.lastname: Beaujean
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosenbaum
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Müller
authors.forename: Jacques J
authors.initials: JJ
authors.lastname: Willemsen
authors.forename: Jacques
authors.initials: J
authors.lastname: Lenders
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology; D006133:Growth Substances / Q000096:biosynthesis*; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016501:Neurites / Q000502:physiology; D009479:Neuropeptides / Q000096:biosynthesis* / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000166:cytology / Q000502:physiology*; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C495403:Adcyap1 protein, rat; D002395:Catecholamines; D016895:Culture Media, Serum-Free; D006133:Growth Substances; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D003907:Dexamethasone