An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite.

Our recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days.

Activity of AMP-regulated protein kinase and AMP-deaminase in the heart of mice fed high-fat diet.

AMP-regulated protein kinase (AMPK) is involved in numerous regulatory processes and its role in control of cardiac energy metabolism is particularly important. This activity could be affected by AMP-deaminase (AMPD) since substrate of AMPD is AMPK activator. Hearts of male mouse, fed for six weeks with normal or high-fat diet, were fractionated to enrich AMPK activity.

Effect of 4-pyridone-3-carboxamide ribonucleoside (4PYR)-potential cardiovascular toxin in perfused rat heart.

We recently described a new nicotinamide derivative: 4-pyridone-3-carboxamide ribonucleoside (4PYR) and its conversion to intracellular metabolites (4PYR monophosphate: 4PYMP and 4PYR adenylate diphosphate: 4PYRAD). The aim of this study was to clarify the metabolism and physiological effects of brief exposure to 4PYR in perfused rat heart. Rat hearts were perfused in Langendorff mode.

Effect of AMP-deaminase 3 knock-out in mice on enzyme activity in heart and other organs.

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.

AMP deaminase 1 gene polymorphism and heart disease-a genetic association that highlights new treatment.

Nucleotide metabolism and signalling is directly linked to myocardial function. Therefore analysis how diversity of genes coding nucleotide metabolism related proteins affects clinical progress of heart disease could provide valuable information for development of new treatments. Several studies identified that polymorphism of AMP deaminase 1 gene (AMPD1), in particular the common C34T variant of this gene was found to benefit patients with heart failure and ischemic heart disease.