Elevated hexokinase increases cardiac glycolysis in transgenic mice

Liang, Qiangrong; Donthi, Rajakumar V.; Kralik, Patricia M.; Epstein, Paul N.

doi:10.1016/s0008-6363(01)00495-3

Cited by 25 publications

(23 citation statements)

References 34 publications

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“…These results are commensurate with studies using over-expression of yeast cardiac HK in cardiac low-flow IR, 34 and suggest that the glucose phosphorylating capacity of the heart is not a critical determinant of active force production, and recovery thereof following IR. We did observe a non-significant trend towards increased irreversible damage with reductions in HKII as LDH release during reperfusion was 30 -55% higher in the HK þ/2 heart.…”

Section: Discussionsupporting

confidence: 82%

“…In contrast to no-flow ischaemia, where glycolysis is halted due to accumulation of metabolic end-products, low-flow ischaemia allows for continuous glycolysis-from-exogenous glucose, and thus glucose phosphorylation, during ischaemia. 33,34 It therefore allows evaluation of the effect of possible diminished glucose phosphorylation in the HK þ/2 hearts on the developing IR injury. In addition, low-flow ischaemia models more closely reflects the clinical condition of myocardial infarction, where residual flow is often present, 35 than a no-flow ischaemia model.…”

Section: Discussionmentioning

confidence: 99%

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The effect of standard chow and reduced hexokinase II on growth, cardiac and skeletal muscle hexokinase and low-flow cardiac ischaemia–reperfusion injury

et al. 2011

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In the present study, we examined whether standard chow (SDS versus Purina 5001; both low fat, high carbohydrate) and reductions in hexokinase (HK) II (wild-type versus HKII þ/2 mice) affect (1) growth parameters, (2) HK levels in cardiac and skeletal muscle and (3) low-flow cardiac ischaemia -reperfusion (IR) injury. Total HK activity and HKI and HKII expressions were determined, and low-flow IR injury was examined in isolated hearts subjected to 40 min 5% low-flow ischaemia and 120 min reperfusion. Standard chow, but not HKII reductions, significantly affected body weight, heart weight and cardiac hypertrophy. Both standard chow and reduced HKII diminished total cardiac and skeletal muscle HK activity. For the heart, the Purina chow-induced decrease in total HK activity was through decreases in HKI expression, whereas for skeletal muscle post-translational mechanisms are suggested. Both standard chow and reduced HKII demonstrated a non-significant trend for affecting cardiac IR damage. However, the low-flow ischaemia model was associated with mild sublethal injury only ( 1% cell death). In conclusion, standard chow affects body weight, heart weight and HK activity and HKI expression in the heart, without altering HKII expression. This implicates standard chow as an important factor in genomic, physiological research models and demonstrates that large differences in fat or carbohydrates in the diet are not necessary to affect growth. In a cardiac low-flow IR model, resulting in only mild injury, standard chow or reduced HKII does not significantly affect IR damage.Keywords: Nutrition, body weight, cardiology, pathology, perfused organ Laboratory Animals 2011; 45: 160-166. DOI: 10.1258/la.2011.010096To our knowledge, standard chow has received little attention in the field of animal experimentation. In contrast, much attention has been given to diets that differ largely in fat or carbohydrates, comparing e.g. low-fat with high-fat diets or low-carbohydrate with high-carbohydrate diets. However, often these diets not only differ in their fat or carbohydrate composition but also in many other components because diets are obtained from different suppliers. 1 -4 Uncertainty then exists as to whether observed effects can be ascribed to alterations in the main constituent (fat or carbohydrate) or to differences in the background standard chow used. Obviously, information is needed concerning the effects that standard chow per se may have on growth and other physiological parameters. We examined this question using wild-type (WT) and HK þ/2 mice. The HK þ/2 mice were shown to have a 50% reduction in hexokinase (HK) II activity in adipose, skeletal and heart tissues, without an effect on HKI activity.5 However, our own initial results with the HK þ/2 mice on HK activity did not show a significant difference between WT and HK þ/2 hearts. Interestingly, a recent study 1 demonstrated that difference in cardiac HKII content between WT and HK þ/2 hearts disappeared when animal nutrition was changed from low-fat to h...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

The effect of standard chow and reduced hexokinase II on growth, cardiac and skeletal muscle hexokinase and low-flow cardiac ischaemia–reperfusion injury

et al. 2011

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“…In addition to structural changes in the myocardium, an altered utilization of cardiac metabolic substrate glucose is recognized as one of the biochemical hallmarks of the hypertrophied and failing heart (42). In the fetal heart, glucose is the primary cardiac substrate while fatty acid metabolism is reduced due to carnitine deficiency and delayed maturation of enzymes involved in fatty acid oxidation.…”

Section: Significance and Backgroundmentioning

confidence: 99%

“…Langendorffperfusions were carried out as we previously described (41,42). The heart was rapidly canulated through the aorta and retrogradely perfused at 2 mllmin with Krebs-Henseleit buffer (KH) consisting of 120 mM NaCl, 20 mM NaHC0 3 , 4.6 mM KCI, 1.2 mM KH2P04, 1.2 mM MgCh, 1.25 mM CaCh, 5 mM glucose.…”

Section: Cardiac Perfusionmentioning

confidence: 99%

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Elevation of cardiac glycolysis reduces pyruvate dehydrogenase but increases glucose oxidation.

Wang¹

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Insulin and Ischemia Stimulate Glycolysis by Acting on the Same Targets Through Different and Opposing Signaling Pathways

Hue¹,

Beauloye

Marsin

et al. 2002

Journal of Molecular and Cellular Cardiology

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Elevated hexokinase increases cardiac glycolysis in transgenic mice

Abstract: These results demonstrate that glucose phosphorylation is a key step in determining cardiac glucose metabolism under oxidative conditions.

Cited by 25 publications

References 34 publications

The effect of standard chow and reduced hexokinase II on growth, cardiac and skeletal muscle hexokinase and low-flow cardiac ischaemia–reperfusion injury

The effect of standard chow and reduced hexokinase II on growth, cardiac and skeletal muscle hexokinase and low-flow cardiac ischaemia–reperfusion injury

Elevation of cardiac glycolysis reduces pyruvate dehydrogenase but increases glucose oxidation.

Insulin and Ischemia Stimulate Glycolysis by Acting on the Same Targets Through Different and Opposing Signaling Pathways

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