The induction of cardiac ornithine decarboxylase by β2-adrenergic agents is associated with calcium channels and phosphorylation of ERK1/2

• Published in: Journal of cellular biochemistry 2013-09, Vol.114 (9), p.1978-1986
• Main Authors: López-Contreras, Andrés J., de la Morena, Maria Eugenia, Ramos-Molina, Bruno, Lambertos, Ana, Cremades, Asunción, Peñafiel, Rafael
• Format: Article
• Language: English
• Subjects: Adrenergic Agents - pharmacology; Animals; BETA-ADRENERGIC AGENTS; Blotting, Western; Calcium Channels - genetics; Calcium Channels - metabolism; CREB; L-CALCIUM CHANNELS; Male; MAP KINASES; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; ORNITHINE DECARBOXYLASE; Ornithine Decarboxylase - genetics; Ornithine Decarboxylase - metabolism; Phosphorylation - drug effects; POLYAMINES; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.24540

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. J. Cell. Biochem. 114: 1978–1986, 2013. © 2013 Wiley Periodicals, Inc.