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Title: Cyclic AMP agonists increase levels of insulin-like growth factor (IGF) binding protein-6 in PC12 rat phaeochromocytoma cells.
Austin Authors: Bach, Leon A;Leeding, K S;Leng, S L
Affiliation: University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia
Issue Date: 1-Jun-1998
Publication information: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society; 8(3): 265-71
Abstract: The predominant insulin-like growth factor binding protein (IGFBP) synthesized by PC12 rat phaeochromocytoma cells is IGFBP-6. Since cAMP agonists regulate IGFBP-6 in other cells, and they may increase neurite outgrowth and catecholaminergic enzyme expression in PC12 cells, we studied regulation of IGFBP-6 by these agents. After 72 h incubation, forskolin and 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) both increased IGFBP-6 protein levels in conditioned media to maximum levels of 231 +/- 40 and 275 +/- 30%, respectively. Incubation with forskolin resulted in a small, transient rise in IGFBP-6 mRNA levels which was insufficient to account for the increased protein levels. The increased protein levels also could not be attributed to increased cell number, protection of IGFBP-6 from proteolysis or release of IGFBP-6 from a cell-associated reservoir. These findings suggest that increased protein levels may have been due to increased translation of mRNA. Co-incubation of forskolin with dexamethasone (which decreases IGFBP-6 protein and mRNA) demonstrated that the effects of the latter were dominant. The effects of cAMP agonists and IGF-II, which increases IGFBP-6 protein but not mRNA levels, were not inhibited by rapamycin, suggesting that p70 S6 kinase is not involved. The effects of cAMP agonists on IGFBP-6 levels were not directly correlated with neurite outgrowth. These findings extend our knowledge of the molecular basis of the regulation of IGFBP-6 by cAMP agonists, and indicate a novel action of these agents in PC12 cells.
Gov't Doc #: 10984315
Type: Journal Article
Subjects: Animals
Cell Division.drug effects
Cyclic AMP.agonists.analogs & derivatives.pharmacology
Dose-Response Relationship, Drug
Extracellular Matrix.drug effects.metabolism
Insulin-Like Growth Factor Binding Protein 6.drug effects.genetics.metabolism
Insulin-Like Growth Factor II.pharmacology
Neurites.drug effects
PC12 Cells.drug effects.metabolism
Appears in Collections:Journal articles

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