Development of Enzymes of Energy Metabolism in Rat Heart

BackgroundIt is well established that the immature myocardium preferentially utilises non-oxidative energy-generating pathways. It exhibits low energy-transfer capacity via the creatine kinase (CK) shuttle, reflected in phosphocreatine (PCr), total creatine and CK levels that are much lower than those of adult myocardium. The mechanisms leading to gradually increasing energy transfer capacity during maturation are poorly understood. Creatine is not synthesised in the heart, but taken up exclusively by the action of the creatine transporter protein (CrT). To determine whether this transporter is ontogenically regulated, the present study serially examined CrT gene expression pattern, together with creatine uptake kinetics and resulting myocardial creatine levels, in rats over the first 80 days of age.ResultsRats were studied during the late prenatal period (-2 days before birth) and 7, 13, 21, 33, 50 and 80 days after birth. Activity of cardiac citrate synthase, creatine kinase and its isoenzymes as well as lactate dehydrogenase (LDH) and its isoenzymes demonstrated the well-described shift from anaerobic towards aerobic metabolism. mRNA levels of CrT in the foetal rat hearts, as determined by real-time PCR, were about 30% of the mRNA levels in the adult rat heart and gradually increased during development. Creatine uptake in isolated perfused rat hearts increased significantly from 3.0 nmol/min/gww at 13 days old to 4.9 nmol/min/gww in 80 day old rats. Accordingly, total creatine content in hearts, measured by HPLC, increased steadily during maturation (30 nmol/mg protein (-2 days) vs 87 nmol/mg protein (80 days)), and correlated closely with CrT gene expression.ConclusionsThe maturation-dependant alterations of CK and LDH isoenzyme activities and of mitochondrial oxidative capacity were paralleled by a progressive increase of CrT expression, creatine uptake kinetics and creatine content in the heart.

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“…A rise in mitochondrial numbers is consistent with previous studies [22] and reflects the increased energy demand of mature myocardium.…”

Section: Discussionsupporting

confidence: 92%

Changes in creatine transporter function during cardiac maturation in the rat

et al. 2010

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“…Myocardial HK activity differs among species and exhibits the transmural gradient [48,49]. It was reported that HK exhibits the maximal enzyme activity in the heart during the fetal period and only moderate changes occur during postnatal life [50,51]. Although higher activity of HK in the RV compared to the LV was found in young rats [49,51], other studies did not detect any significant right-to-left ventricular difference [52,53,54] according to results of the present work.…”

Section: Discussionmentioning

confidence: 99%

Right-To-Left Ventricular Differences in the Expression of Mitochondrial Hexokinase and Phosphorylation of Akt

Waskova-Arnostova

Elsnicová²,

Kasparova³

et al. 2013

Cell Physiol Biochem

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Background/Aims: Hexokinase (HK) is a key glycolytic enzyme which promotes the maintenance of glucose homeostasis in cardiomyocytes. HK1 isoform is predominantly bound to the outer mitochondrial membrane and highly supports oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. HK2 isoform is under physiological conditions predominantly localized in the cytosol and upon stimulation of PI3K/ Akt pathway associates with mitochondria and thus can prevent apoptosis. The purpose of this study was to investigate expression and subcellular localization of both HK isoforms in left (LV) and right (RV) heart ventricles of adult male Wistar rats. Methods: Real-Time RT-PCR, Western blotting, and quantitative immunofluorescence microscopy were used. Results: Our results showed a significantly higher expression of both HK1 and HK2 at mRNA and protein levels in the RV compared to the LV. These findings were corroborated by immunofluorescence staining which revealed substantially higher fluorescence signals of both HKs in the RV than in the LV. The ratios of phospho-Ser473-Akt/non-phospho-Akt and phospho-Thr308-Akt/non-phospho-Akt were also markedly higher in the RV than in the LV. Conclusion: These results suggest that the RV has a higher activity of aerobic glycolytic metabolism and may be able to respond faster and more powerfully to stressful stimuli than the LV.

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“…It is belived, that this isoform permits rapid ADP/ATP exchange across the inner mitochondria] membrane [30, 311. The data presented here demonstrate clearly that changes in the matrix adenine nucleotides and in the AAC protein are important factors in the postnatal maturation of oxidative phosphorylation. On the other hand, enrichment of the F,F,-ATP synthase [24, 251, of the respiratory chain complexes [32,331, of the hydrogen-supplying enzymes (citric acid cycle enzymes [ 321, pyruvate dehydrogenase complex [ 341, P-oxidation enzymes [35]), the mitochondrial creatine kinase [36] in mitochondria and the reduction of the passive proton permeability of the inner mitochondrial membrane [8] also contribute to this process. Interestingly, the reduction in the passive proton permeability of the inner mitochondrial membrane during postnatal development has been attributed to the interaction of the AAC with the matrix adenine nucleotides [37].…”

Section: Discussionmentioning

confidence: 99%

Expression of the ADP/ATP Carrier and Expansion of the Mitochondrial (ATP + ADP) Pool Contribute to Postnatal Maturation of the Rat Heart

Schönfeld

Schild

Bohnensack

1996

European Journal of Biochemistry

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The role of the ADP/ATP carrier (AAC), a key protein of the mitochondrial ATP-generating system, is not clear during postnatal rat heart development. To elucidate this role, the phosphorylating respiration (state 3), the activity and the content of AAC, the size of the exchangeable mitochondrial (ATP + ADP) pool and the control of AAC over respiration at state 3 were measured in mitochondria isolated from rat hearts at various postnatal ages.There was a 5-fold increase in the AAC activity from newborn to aged rat hearts, which was paralleled by a 1 .S-fold increase in state 3 respiration. At birth, the AAC and the F,F,-ATP synthase exerted about 80 % of the control over phosphorylating respiration (state 3 : flux control coefficients 0.39 -C 0.04 and 0.38 t 0.08). The strong increase in the AAC activity was partly caused by the doubling of the protein content. In addition, the turnover number of AAC increased by a factor of 2.5 due to the expansion of the (ATP + ADP) pool from 3.420.9 to 10.62 1.5 nmol . mg protein-'. The data strongly indicate that the increase in the AAC activity is an essential step in the postnatal maturation of rat heart mitochondria.Keywords: ADP/ATP carrier; adenine nucleotide ; F,F, -ATP synthase; heart mitochondria; maturation.At birth the mammalian heart is functionally not full developed. Quantitative ultrastructural analysis of the neonatal myocardium revealed a low number of small-sized mitochondria, a sparse sarcoplasmatic reticulum, less myofibrillar protein, and the absence of t-tubules compared with adults [l-41. During perinatal development there is an increase in the contractility and a shift from glycolytic to oxidative metabolism in heart muscle [5]. For liver it has been demonstrated that the energy-linked functions of mitochondria in neonatal tissue are in an unmatured state (for reviews see [6,7]), as indicated by a low oxidative phosphorylation efficiency, a low rate of phosphorylating respiration (state 3) and a high passive proton permeability of the inner mitochondrial membrane [S]. During the postnatal maturation the concentration of matrix adenine nucleotides increased due to a net uptake of adenine nucleotides from the cytosol and the expression of key proteins of the oxidative phosphorylation is stimulated [6, 71. One of the key proteins is the ADP/ATP carrier (abbreviated here as AAC), a protein (=30 kDa) intrinsic to the inner mitochondrial membrane catalyzing the 1:1 exchange of cytosolic ADP and matrix ATP in the process of oxiCorrespondence to

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Development of Enzymes of Energy Metabolism in Rat Heart

Cited by 11 publications

References 28 publications

Changes in creatine transporter function during cardiac maturation in the rat

Changes in creatine transporter function during cardiac maturation in the rat

Right-To-Left Ventricular Differences in the Expression of Mitochondrial Hexokinase and Phosphorylation of Akt

Expression of the ADP/ATP Carrier and Expansion of the Mitochondrial (ATP + ADP) Pool Contribute to Postnatal Maturation of the Rat Heart

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