title: cAMP-responsive element-binding protein (CREB) and cAMP co-regulate activator protein 1 (AP1)-dependent regeneration-associated gene expression and neurite growth.
abstract: To regenerate damaged axons, neurons must express a cassette of regeneration-associated genes (RAGs) that increases intrinsic growth capacity and confers resistance to extrinsic inhibitory cues. Here we show that dibutyrl-cAMP or forskolin combined with constitutive-active CREB are superior to either agent alone in driving neurite growth on permissive and inhibitory substrates. Of the RAGs examined, only arginase 1 (Arg1) expression correlated with the increased neurite growth induced by the cAMP/CREB combination, both of which were AP1-dependent. This suggests that cAMP-induced AP1 activity is necessary and interacts with CREB to drive expression of RAGs relevant for regeneration and demonstrates that combining a small molecule (cAMP) with an activated transcription factor (CREB) stimulates the gene expression necessary to enhance axonal regeneration.
authors.affiliation: From the Burke-Cornell Medical Research Institute, White Plains, New York 10605 and.
authors.forename: Thong C
authors.initials: TC
authors.lastname: Ma
authors.affiliation: the Instituto de Neurociencias de Alicante (Universidad Miguel Hernández de Elche-Consejo Superior de Investigaciones Científicas), San Juan de Alicante, 03550 Alicante, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Barco
authors.affiliation: From the Burke-Cornell Medical Research Institute, White Plains, New York 10605 and.
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Ratan
authors.affiliation: From the Burke-Cornell Medical Research Institute, White Plains, New York 10605 and diw2004@med.cornell.edu.
authors.forename: Dianna E
authors.initials: DE
authors.lastname: Willis
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D019004:Galanin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D008856:Microscopy, Fluorescence; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018808:Transcription Factor AP-1; D019004:Galanin; D000242:Cyclic AMP; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: AP1 Transcription Factor (AP-1); Cyclic AMP (cAMP); Regeneration; Regeneration-associated Gene; Transcription; cAMP Response Element-binding Protein (CREB)