High-energy phosphotransfer in the failing mouse heart: role of adenylate kinase and glycolytic enzymes.

Abstract

AIMS:

To measure the activity of the key phosphotransfer enzymes creatine kinase (CK), adenylate kinase (AK), and glycolytic enzymes in two common mouse models of chronic heart failure.

METHODS AND RESULTS:

C57BL/6 mice were subjected to transverse aortic constriction (TAC), myocardial infarction induced by coronary artery ligation (CAL), or sham operation. Activities of phosphotransfer enzymes CK, AK, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK), and pyruvate kinase were assessed spectrophotometrically. Mice were characterized by echocardiography or magnetic resonance imaging 5- to 8-week post-surgery and selected for the presence of congestive heart failure. All mice had severe left ventricular hypertrophy, impaired systolic function and pulmonary congestion compared with sham controls. A significant decrease in myocardial CK and maximal CK reaction velocity was observed in both experimental models of heart failure. However, the activity of AK and its isoforms remained unchanged, despite a reduction in its protein expression. In contrast, the activities of glycolytic phosphotransfer mediators GAPDH and PGK were 19 and 12% higher in TAC, and 31 and 23% higher in CAL models, respectively.

CONCLUSION:

Chronic heart failure in the mouse is characterized by impaired CK function, unaltered AK, and increased activity of glycolytic phosphotransfer enzymes. This pattern of altered phosphotransfer activity was observed independent of the heart failure aetiology.

• Authors: Dunja Aksentijević, Craig A Lygate, Kimmo Makinen, Sevasti Zervou, Liam Sebag-Montefiore, Debra Medway, Hannah Barnes, Jurgen E Schneider, Stefan Neubauer
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 12 Issue 12 Pg. 1282-9 (Dec 2010) ISSN: 1879-0844 [Electronic] England
• PMID: 20940173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphotransferases
• Creatine Kinase
• Adenylate Kinase

Topics

• Adenylate Kinase (metabolism)
• Animals
• Blotting, Western
• Creatine Kinase (metabolism)
• Disease Models, Animal
• Heart Failure (diagnostic imaging, enzymology, metabolism)
• Hemodynamics
• Humans
• Hypertrophy, Left Ventricular (diagnostic imaging, enzymology, metabolism)
• Ligation
• Male
• Mice
• Mice, Inbred C57BL
• Phosphorylation
• Phosphotransferases (metabolism)
• Signal Transduction (physiology)
• Statistics as Topic
• Ultrasonography
• Ventricular Function, Left