The effects of inhibition of oxidative phosphorylation and glycolysis on contractility and high-energy phosphate content in cultured chick heart cells.

Doorey, Andrew J.; Barry, William H.

doi:10.1161/01.res.53.2.192

Cited by 60 publications

(31 citation statements)

References 56 publications

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“…The increased dependence of hypertrophied myocardium for glucose utilization may be related to an increased activity of glycolytic enzymes (8,46) as well as a switch to the fetal pattern of enhanced expression of the GLUT 1 basal transporter relative to the GLUT 4 insulinresponsive transporter (47). Taken together, these observations lend support that utilization of glucose as an energy substrate in hypertrophied myocardium may simulate the immature pattern of enhanced dependence on glycolysis for cardiac ATP production which has been observed in neonatal hearts (48) and embryonic cultured myocytes (49).…”

Section: Discussionmentioning

confidence: 69%

Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.

Kagaya¹,

Weinberg²,

Ito³

et al. 1995

J. Clin. Invest.

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We tested the hypothesis' that glycolytic inhibition by 2-deoxyglucose causes greater impairment of diastolic relaxation and intracellular calcium handling in well-oxygenated hypertrophied adult rat myocytes compared with control myocytes. We simultaneously measured cell motion and intracellular free calcium concentration ([Ca2]I,) with indo-1 in isolated paced myocytes from aortic-banded rats and sham-operated rats. There was no difference in either the end-diastolic or peak-systolic [Ca2"]I between control and hypertrophied myocytes (97±18 vs. 105±15 nM, 467±92 vs. 556±67 nM, respectively). Myocytes were first superfused with oxygenated Hepes-buffered solution containing 1.2 mM CaC12, 5.6 mM glucose, and 5 mM acetate, and paced at 3 Hz at 360C. Exposure to 20 mM 2-deoxyglucose as substitution of glucose for 15 min caused an upward shift of enddiastolic cell position in both control (n = 5) and hypertrophied myocytes (n = 10) (P < 0.001 vs. baseline), indicating an impaired extent of relaxation. Hypertrophied myocytes, however, showed a greater upward shift in end-diastolic cell position and slowing of relaxation compared with control myocytes (A144±28 vs. 55±15% of baseline diastolic position, P < 0.02). Exposure to 2-deoxyglucose increased enddiastolic [Ca2+ ]; in both groups (P < 0.001 vs. baseline), but there was no difference between hypertrophied and control myocytes (218±38 vs. 183±29 nM, respectively). The effects of 2-deoxyglucose were corroborated in isolated oxygenated perfused hearts in which glycolytic inhibition which caused severe elevation of isovolumic diastolic pressure and prolongation of relaxation in the hypertrophied hearts compared with controls. In summary, the inhibition of the glycolytic pathway impairs diastolic relaxation to a greater extent in hypertrophied myocytes than in control myocytes even in well-oxygenated conditions. The severe impairment of diastolic relaxation induced by 2-deoxyglucose in hypertrophied myocytes compared with control myocytes cannot be explained by greater diastolic Ca2" overload, which implicates an increase in myofflament Ca2+-responsiveness as a possible mechanism. (J. Clin.

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Section: Discussionmentioning

confidence: 69%

Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.

Kagaya¹,

Weinberg²,

Ito³

et al. 1995

J. Clin. Invest.

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“…High-energy phosphate levels. The treatment of cultured myocardial cells with either glycolytic (16) or respiratory inhibitors (16) resulted in significant decreases in cellular ATP content versus control ( Table I). As shown in Tables I and II, treatment with iodoacetate resulted in a time dependent decrease in ATP content of the cultured myocardial cells.…”

Section: Resultsmentioning

confidence: 99%

Release of arachidonate from membrane phospholipids in cultured neonatal rat myocardial cells during adenosine triphosphate depletion. Correlation with the progression of cell injury.

Chien¹,

Sen²,

Reynolds³

et al. 1985

J. Clin. Invest.

118

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“…Several of the major observations supporting this idea are the following. Selective inhibition of anaerobic glycolysis and selective inhibition of mitochondrial oxidative phosphorylation have different functional effects, which cannot be attributed to changes in global tissue high-energy phosphate levels (2,33,34). Manipulations of glycolysis markedly affect functional performance and recovery during ischemia/reperfusion or hypoxia/reoxygenation, again in a manner that does not correlate with changes in global tissue high-phosphate levels (35)(36)(37)(38)(39).…”

Section: Perspective 2: Cardiovascular Metabolism As a Physical Spatmentioning

confidence: 99%

Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism

Weiss

Yang

2006

Journal of Lipid Research

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In this review, we examine cardiovascular metabolism from three different, but highly complementary, perspectives. First, from the abstract perspective of a metabolite network, composed of nodes and links. We present fundamental concepts in network theory, including emergence, to illustrate how nature has designed metabolism with a hierarchal modular scale-free topology to provide a robust system of energy delivery. Second, from the physical perspective of a modular spatially compartmentalized network. We review evidence that cardiovascular metabolism is functionally compartmentalized, such that oxidative phosphorylation, glycolysis, and glycogenolysis preferentially channel ATP to ATPases in different cellular compartments, using creatine kinase and adenylate kinase to maximize efficient energy delivery. Third, from the dynamics perspective, as a network of dynamically interactive metabolic modules capable of self-oscillation. Whereas normally, cardiac metabolism exists in a regime in which excitation-metabolism coupling closely matches energy supply and demand, we describe how under stressful conditions, the network can be pushed into a qualitatively new dynamic regime, manifested as cell-wide oscillations in ATP levels, in which the coordination between energy supply and demand is lost. We speculate how this state of "metabolic fibrillation" leads to cell death if not corrected and discuss the implications for cardioprotection.-Weiss, J. N., L. Yang, and Z. Qu. Network perspectives of cardiovascular metabolism. J. Lipid Res. 2006Res. . 47: 2355Res. -2366. Supplementary key words mitochondriaMuscle cells must adapt rapidly to a much wider range of energy demands than most noncontractile cells. For example, the rate of respiration by cardiac muscle increases by a factor of 15-20 between unloaded and maximal workload conditions (1). This requires a very robust metabolic network that can deliver smooth performance over a wide range of parameters. Although we do not yet fully understand how this is accomplished, new systems biology approaches, complemented by network theory and computer modeling studies, are at the threshold of providing new insights.Cardiovascular metabolism can be viewed as a network of interlinked energy-produced pathways (e.g., oxidative phosphorylation, glycolysis, and glycogenolysis), energyconsuming pathways [e.g., myofilament, sarcoplasmic reticulum (SR), and sarcolemma (SL) ATPases], and energydistributing pathways [e.g., creatine kinase (CK) and adenylate kinase (AK)] (Fig. 1A). In this review, we begin by considering metabolism from a highly abstract perspective, as a metabolite network in which substrates/products are represented as nodes and metabolic enzymes are represented as the links between nodes. We present some fundamental concepts in network theory, including the concept of emergence, and discuss how through Darwinian evolution metabolic networks are likely to have evolved a scale-free hierarchal modular topology that ensures the robustness of this most fundamental ...

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The effects of inhibition of oxidative phosphorylation and glycolysis on contractility and high-energy phosphate content in cultured chick heart cells.

Cited by 60 publications

References 56 publications

Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.

Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.

Release of arachidonate from membrane phospholipids in cultured neonatal rat myocardial cells during adenosine triphosphate depletion. Correlation with the progression of cell injury.

Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism

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