Enhanced activity and subcellular redistribution of myocardial hexokinase after acute myocardial infarction

Background: Hexokinase (HK) is known to possess both anti-oxidant and anti-apoptotic properties. This study investigated the behavior of myocardial HK in response to myocardial infarction (MI). Methods: Adult male Wistar rats with various degrees of MI after coronary ligation were examined 4 weeks after operation and were divided dichotomously into small and large MI groups. The activity and subcellular distribution of HK in the non-infarcted myocardium were determined. In parallel, myocardial oxidative stress determined using aconitase activity and malondialdehyde content, and left ventricular function using echocardiography were studied. Results: In the mitochondria and the cytosol, HK activity was enhanced after MI and paralleled the increases in oxidative stress and left ventricular end-diastolic dimension (LVEDD). The enhancement in HK activity varied between subcellular compartments and resulted in an increase in the ratio of cytosol to whole-cell HK activity, which was proportional to oxidative stress and LVEDD. Conclusions: The activities of HK in all subcellular fractions are enhanced in response to MI. However, enhanced proportion of cytosolic HK relative to whole-cell HK activity is associated with higher oxidative stress and LVEDD, suggesting that altered myocardial HK activity and subcellular redistribution might be involved in the pathogenesis of postinfarct heart failure. © 2009 Elsevier Ireland Ltd.