title: Effect of AMP-deaminase 3 knock-out in mice on enzyme activity in heart and other organs.
abstract: Recent findings suggest that inhibition of AMP-deaminase (AMPD) could be effective therapeutic strategy in heart disease associated with cardiac ischemia. To establish experimental model to study protective mechanisms of AMPD inhibition we developed conditional, cardiac specific knock-outs in Cre recombinase system. AMPD3 floxed mice were crossed with Mer-Cre-Mer mice. Tamoxifen was injected to induce Cre recombinase. After two weeks, hearts, skeletal muscle, liver, kidney, and blood were collected and activities of AMPD and related enzymes were analyzed using HPLC-based procedure. We demonstrate loss of more than 90% of cardiac AMPD activity in the heart of AMPD3-/-mice while other enzymes of nucleotide metabolism such as adenosine deaminase, purine nucleoside phosphorylase were not affected. Surprisingly, activity of AMPD was also reduced in the erythrocytes and in the kidney by 20%-30%. No change of AMPD activity was observed in the skeletal muscle and the liver.
authors.affiliation: a Department of Biochemistry and Clinical Physiology , Medical University of Gdansk , Gdansk , Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Rybakowska
authors.forename: Pawel
authors.initials: P
authors.lastname: Romaszko
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zabielska
authors.forename: Jacek
authors.initials: J
authors.lastname: Turyn
authors.forename: Krystian
authors.initials: K
authors.lastname: Kaletha
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Barton
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Slominska
authors.forename: Ryszard T
authors.initials: RT
authors.lastname: Smolenski
mesh_terms: D000659:AMP Deaminase / Q000172:deficiency* / Q000235:genetics*; D000818:Animals; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D051379:Mice; D009206:Myocardium / Q000201:enzymology*; D009928:Organ Specificity
chemical_list: D000659:AMP Deaminase
keywords: AMP-deaminase; AMPD3 homozygous; AMPD3 wild type; Cre recombinase; cardioprotection