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Article: Glucocorticoid regulation of an insulin-like growth factor-binding protein-4 protease produced by a rat neuronal cell line

TitleGlucocorticoid regulation of an insulin-like growth factor-binding protein-4 protease produced by a rat neuronal cell line
Authors
Issue Date1994
PublisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.org
Citation
Endocrinology, 1994, v. 135 n. 4, p. 1328-1335 How to Cite?
AbstractInsulin-like growth factor-binding protein-4 (IGFBP-4) is expressed in distinct regions in the rodent brain from the perinatal period into adulthood and is postulated to modulate the action of the insulin-like growth factors (IGFs) in vivo. This study was initiated to examine the regulation of IGF- binding protein-4 (IGFBP-4) in B104 cells, a rat neuronal cell line in which IGFBP-4 is the predominant secreted IGFBP. Exposure of B104 monolayer cultures to dexamethasone reduced native IGFBP-4 abundance to less than 10% of that in control medium by 48 h. Immunoblots showed that the decline in intact 24-kilodalton IGFBP-4 was accompanied by an increase in a 16- kilodalton immunoreactive fragment. In addition, IGFBP-4 proteolytic activity in medium was increased after exposure of the cells to dexamethasone. The protease was calcium dependent and appeared to be of the serine protease class, because activity could be inhibited by phenylmethylsulfonylfluoride and aprotinin, but not antipain, leupeptin, or pepstatin. Although the proteolytically modified IGFBP-4 retained the ability to bind IGFs, the affinities were approximately 13- and 20-fold lower for IGF-I and IGF-II, respectively. These data indicate that B104 cells produce an IGFBP-4 protease that is regulated by glucocorticoids. The actions of this protease reduce the affinity of IGFBP-4 for the IGFs without abolishing binding. Because both the IGFs and glucocorticoids have important roles in brain development, it is possible that some glucocorticoid actions in the brain could be mediated by proteolysis of IGFBP-4, which, in turn, would alter IGF action.
Persistent Identifierhttp://hdl.handle.net/10722/170271
ISSN
2015 Impact Factor: 4.159
2015 SCImago Journal Rankings: 2.363
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, PTen_US
dc.contributor.authorWu, Jen_US
dc.contributor.authorBanach, Wen_US
dc.contributor.authorChernausek, SDen_US
dc.date.accessioned2012-10-30T06:07:06Z-
dc.date.available2012-10-30T06:07:06Z-
dc.date.issued1994en_US
dc.identifier.citationEndocrinology, 1994, v. 135 n. 4, p. 1328-1335en_US
dc.identifier.issn0013-7227en_US
dc.identifier.urihttp://hdl.handle.net/10722/170271-
dc.description.abstractInsulin-like growth factor-binding protein-4 (IGFBP-4) is expressed in distinct regions in the rodent brain from the perinatal period into adulthood and is postulated to modulate the action of the insulin-like growth factors (IGFs) in vivo. This study was initiated to examine the regulation of IGF- binding protein-4 (IGFBP-4) in B104 cells, a rat neuronal cell line in which IGFBP-4 is the predominant secreted IGFBP. Exposure of B104 monolayer cultures to dexamethasone reduced native IGFBP-4 abundance to less than 10% of that in control medium by 48 h. Immunoblots showed that the decline in intact 24-kilodalton IGFBP-4 was accompanied by an increase in a 16- kilodalton immunoreactive fragment. In addition, IGFBP-4 proteolytic activity in medium was increased after exposure of the cells to dexamethasone. The protease was calcium dependent and appeared to be of the serine protease class, because activity could be inhibited by phenylmethylsulfonylfluoride and aprotinin, but not antipain, leupeptin, or pepstatin. Although the proteolytically modified IGFBP-4 retained the ability to bind IGFs, the affinities were approximately 13- and 20-fold lower for IGF-I and IGF-II, respectively. These data indicate that B104 cells produce an IGFBP-4 protease that is regulated by glucocorticoids. The actions of this protease reduce the affinity of IGFBP-4 for the IGFs without abolishing binding. Because both the IGFs and glucocorticoids have important roles in brain development, it is possible that some glucocorticoid actions in the brain could be mediated by proteolysis of IGFBP-4, which, in turn, would alter IGF action.en_US
dc.languageengen_US
dc.publisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.orgen_US
dc.relation.ispartofEndocrinologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCarrier Proteins - Analysis - Metabolism - Physiologyen_US
dc.subject.meshCulture Media, Conditioned - Pharmacologyen_US
dc.subject.meshDexamethasone - Pharmacologyen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshGlucocorticoids - Pharmacologyen_US
dc.subject.meshHydrogen-Ion Concentrationen_US
dc.subject.meshInsulin-Like Growth Factor Binding Protein 4en_US
dc.subject.meshInsulin-Like Growth Factor I - Metabolism - Pharmacologyen_US
dc.subject.meshInsulin-Like Growth Factor Ii - Analysis - Metabolismen_US
dc.subject.meshMetalloendopeptidases - Analysis - Metabolism - Physiologyen_US
dc.subject.meshNeuroblastoma - Chemistry - Metabolism - Pathologyen_US
dc.subject.meshNeurons - Chemistry - Metabolism - Pathologyen_US
dc.subject.meshPregnancy-Associated Plasma Protein-Aen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshRna, Messenger - Analysis - Geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshTemperatureen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.titleGlucocorticoid regulation of an insulin-like growth factor-binding protein-4 protease produced by a rat neuronal cell lineen_US
dc.typeArticleen_US
dc.identifier.emailCheung, PT:ptcheung@hkucc.hku.hken_US
dc.identifier.authorityCheung, PT=rp00351en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1210/en.135.4.1328en_US
dc.identifier.pmid7523095-
dc.identifier.scopuseid_2-s2.0-0027994208en_US
dc.identifier.volume135en_US
dc.identifier.issue4en_US
dc.identifier.spage1328en_US
dc.identifier.epage1335en_US
dc.identifier.isiWOS:A1994PK87700006-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCheung, PT=7202595465en_US
dc.identifier.scopusauthoridWu, J=7409252482en_US
dc.identifier.scopusauthoridBanach, W=6701544749en_US
dc.identifier.scopusauthoridChernausek, SD=7005403226en_US

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