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.
| Original language | English |
|---|---|
| Book series | Journal of Cellular Biochemistry. Supplement |
| Volume | 114 |
| Issue number | 9 |
| Pages (from-to) | 1978-86 |
| Number of pages | 9 |
| ISSN | 0733-1959 |
| DOIs | |
| Publication status | Published - Sept 2013 |
| Externally published | Yes |
Keywords
- Adrenergic Agents
- Animals
- Blotting, Western
- Calcium Channels
- Male
- Mice
- Mice, Inbred BALB C
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Ornithine Decarboxylase
- Phosphorylation
- Reverse Transcriptase Polymerase Chain Reaction