Subject(s)
Cyclooxygenase 1/genetics , Hemorrhagic Disorders/genetics , Loss of Function Mutation , Mutation, Missense , Platelet Activation/genetics , Protein Processing, Post-Translational/genetics , Adolescent , Asian People/genetics , Cyclooxygenase 1/deficiency , Cyclooxygenase 1/metabolism , Female , Genes, Dominant , Glycosylation , HEK293 Cells , Hemorrhagic Disorders/blood , Heterozygote , Humans , Phenotype , Platelet Activation/physiologyABSTRACT
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 ß2 -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 ß2 -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 ß2 -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.
