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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 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/9252 | Journal: | Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society | URL: | https://pubmed.ncbi.nlm.nih.gov/10984315 | Type: | Journal Article | Subjects: | Animals Cell Division.drug effects Colforsin.pharmacology Cyclic AMP.agonists.analogs & derivatives.pharmacology Dexamethasone.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 Rats Sirolimus.pharmacology Thionucleotides.pharmacology |
Appears in Collections: | Journal articles |
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