Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC28
Expression of the amiloride binding protein 1 (Abp1) is stimulated in response to hypoxia and myocardial infarction
K. M. Kirschner1, J. Braun1, H. Scholz1
1. Institut fuer Vegetative Physiologie, Charit
Putrescine is a polyamine, which is important for normal cell growth and division. Putrescine formation is enhanced by myocardial ischemia presumably due to increased ornithine decarboxylase (ODC) activity. The goal of this study was to assess the role of the diamine oxidase, ABP1, in regulating putrescine degradation in the ischemic rat heart. For this purpose, adult rats were anaesthetised using chloralhydrate (400 mg/kg) and subjected either to left coronary artery ligation or sham-surgery (1). Abp1 mRNA was measured by real-time RT-PCR. Twenty-four hours after surgery, a 10-fold increase of Abp1 transcripts was observed in the hearts of rats with myocardial infarction compared to sham-operated animals (students t-test, P<0.001, n=5). ODC expression was not significantly changed at 24 hours after infarction. Consistently, exposure of mice to 8% O2 for 6 hours (2) caused an 11-fold increase of Abp1 mRNA in the hearts (P<0.05, n=5) with no significant changes of ODC transcripts. Hearts were collected after mice had been killed. Abp1 mRNA levels were also significantly increased in several cell lines grown at 1% O2 for 24 h. A luciferase reporter construct carrying the promoter of the Abp1 gene was stimulated approx. 3.5-fold in transfected C2C12 myoblasts at 1% O2. Abp1 mRNA levels were increased 10-fold upon in vitro differentiation of C2C12 cells to myotubes. Inhibition of Abp1 by amiloride (100 µM) prevented the in vitro differentiation of C2C12 myoblasts. In conclusion, cardiac expression of Abp1 is stimulated in response to hypoxia and myocardial infarction. It is suggested that enhanced Abp1 expression has a role in tissue remodelling after myocardial ischemia through regulating putrescine metabolism.
Where applicable, experiments conform with Society ethical requirements