title: The induction of cardiac ornithine decarboxylase by β2 -adrenergic agents is associated with calcium channels and phosphorylation of ERK1/2.
abstract: The role that the induction of cardiac ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, by beta-adrenergic agents may have in heart hypertrophy is a controversial issue. Besides, the signaling pathways related to cardiac ODC regulation have not been fully elucidated. Here we show that in Balb C mice the stimulation of cardiac ODC activity by adrenergic agents was mainly mediated by β2 -adrenergic receptors, and that this induction was lower in the hypertrophic heart. Interestingly, this stimulation was abolished by the L-calcium channel antagonists verapamil and nifedipine. In addition, whereas the treatment with β2 -adrenergic agents was associated to both the increases in ODC, ODC-antizyme inhibitor 1 (AZIN1), c-fos and c-myc mRNA levels and the phosphorylation of CREB and MAP kinases ERK1 and ERK2 (ERK1/2), the co-treatment with L-calcium channel blockers differentially prevented most of these changes. These results suggest that the stimulation of cardiac ODC by β2 -adrenergic agents is associated with the activation of MAP kinases through the participation of L-calcium channels, and that by itself p-CREB does not appear to be sufficient for the transcriptional activation of ODC. In addition, post-translational mechanisms related with the induction of AZIN1 appear to be related to the increase of cardiac ODC activity.
authors.affiliation: Faculty of Medicine, Department of Biochemistry and Molecular Biology B and Immunology, University of Murcia, Murcia, Spain.
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: López-Contreras
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: de la Morena
authors.forename: Bruno
authors.initials: B
authors.lastname: Ramos-Molina
authors.forename: Ana
authors.initials: A
authors.lastname: Lambertos
authors.forename: Asunción
authors.initials: A
authors.lastname: Cremades
authors.forename: Rafael
authors.initials: R
authors.lastname: Peñafiel
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018663:Adrenergic Agents; D015220:Calcium Channels; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009955:Ornithine Decarboxylase
keywords: BETA-ADRENERGIC AGENTS; CREB; L-CALCIUM CHANNELS; MAP KINASES; ORNITHINE DECARBOXYLASE; POLYAMINES