Abstract 345: Dramatic ATP Depletion Without Concomitant Declines in ATP Synthesis Rates Suggests Impaired Energy Metabolism Mechanisms in Adrenergic-Deficient Mouse Embryos

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jessica N Peoples ◽  
Candice Baker ◽  
Steven Ebert
Keyword(s):  
Steady State ◽  
Energy Metabolism ◽  
Embryonic Development ◽  
Atp Synthesis ◽  
Mouse Embryos ◽  
Atp Depletion ◽  
Metabolic Substrates ◽  
Energy Demands ◽  
Cardiac Energy

High cardiac energy demands increase during embryonic development, requiring oxidative phosphorylation converting ADP to ATP in mitochondria to meet these demands. We have recently shown that adrenergic hormones are required to maintain sufficient cardiac energy metabolism during embryonic development, but the specific mechanism(s) underlying this regulation are not known. Mouse embryos lacking adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to targeted loss of the essential dopamine β-hydroxylase ( Dbh ) gene, have remarkably decreased steady-state ATP/ADP ratios. To determine if ATP synthesis was affected, we examined the rate of ATP formation in adrenergic-deficient and control embryonic hearts. Our rate data have shown that despite > 50-fold decrease of steady-state ATP concentrations in Dbh -/- embryos, the rate of ATP synthesis was not significantly different in adrenergic-competent and deficient embryos. This indicates that respiratory complexes in mitochondria are capable of producing ATP in adrenergic-deficient embryos, and suggest that ATP is either consumed at a faster rate than it is produced or its production is limited in vivo due to limited access to metabolic substrates (“starvation”). These findings reveal new mechanistic insights about how adrenergic hormones regulate energy metabolism during embryonic development.

scholarly journals Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation

2015 ◽  
Vol 308 (5) ◽  
pp. E402-E413 ◽  
Author(s):  
Candice N. Baker ◽  
Sarah A. Gidus ◽  
George F. Price ◽  
Jessica N. R. Peoples ◽  
Steven N. Ebert
Keyword(s):  
Energy Metabolism ◽  
Mouse Embryos ◽  
Adrenergic Stimulation ◽  
Energy Demands ◽  
Significant Difference ◽  
Cardiac Energy Metabolism ◽  
Consumption Rates ◽  
Cardiac Energy ◽  
Β Adrenergic Receptors

As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase ( Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh−/−embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development.

scholarly journals The PPARα-PGC-1αAxis Controls Cardiac Energy Metabolism in Healthy and Diseased Myocardium

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Jennifer G. Duncan ◽  
Brian N. Finck
Keyword(s):  
Energy Metabolism ◽  
Transcriptional Control ◽  
Mitochondrial Energy Metabolism ◽  
Multiple Substrates ◽  
Energy Demands ◽  
Expression Of Genes ◽  
Cardiac Energy Metabolism ◽  
Genes Encoding ◽  
Mammalian Myocardium ◽  
Cardiac Energy

The mammalian myocardium is an omnivorous organ that relies on multiple substrates in order to fulfill its tremendous energy demands. Cardiac energy metabolism preference is regulated at several critical points, including at the level of gene transcription. Emerging evidence indicates that the nuclear receptor PPARαand its cardiac-enriched coactivator protein, PGC-1α, play important roles in the transcriptional control of myocardial energy metabolism. The PPARα-PGC-1αcomplex controls the expression of genes encoding enzymes involved in cardiac fatty acid and glucose metabolism as well as mitochondrial biogenesis. Also, evidence has emerged that the activity of the PPARα-PGC-1αcomplex is perturbed in several pathophysiologic conditions and that altered activity of this pathway may play a role in cardiomyopathic remodeling. In this review, we detail the current understanding of the effects of the PPARα-PGC-1αaxis in regulating mitochondrial energy metabolism and cardiac function in response to physiologic and pathophysiologic stimuli.

scholarly journals Effects of NKY-722, a novel calcium antagonist, on the changes of cardiac energy metabolism — an in vivo 31P-MRS study

1992 ◽  
Vol 58 ◽  
pp. 274
Author(s):  
Yuta Kobayashi ◽  
Youko Tanabe ◽  
Kazumasa Shinozuka ◽  
Shuji Takaori ◽  
Keisuke Hattori
Keyword(s):  
Calcium Antagonist ◽  
Energy Metabolism ◽  
31P Mrs ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy

Impairment of Cardiac Energy Metabolism In Vivo Causes Hemodynamic Abnormality and Increases Cardiac Expression of Preproendothelin-1 mRNA

2000 ◽  
Vol 36 ◽  
pp. S128-S131
Author(s):  
Nobuyuki Murakoshi ◽  
Takashi Miyauchi ◽  
Yoshihiko Kakinuma ◽  
Koichi Yuki ◽  
Katsutoshi Goto ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy

scholarly journals Flow Thresholds for Cerebral Energy Disturbance and Na+ Pump Failure as Studied by in vivo 31P and 23Na Nuclear Magnetic Resonance Spectroscopy

1988 ◽  
Vol 8 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Hiroaki Naritomi ◽  
Masahiro Sasaki ◽  
Masaru Kanashiro ◽  
Mitsuhiro Kitani ◽  
Tohru Sawada
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Energy Metabolism ◽  
Magnetic Resonance ◽  
Atp Depletion ◽  
Resonance Spectroscopy ◽  
Pump Failure ◽  
Na Pump ◽  
Pump Activity ◽  
Nuclear Magnetic

The relationships among CBF, cerebral energy metabolism, Na+ pump activity, and electrocorticograms (ECoG) following graded hypotension were studied in 48 gerbils. Energy metabolism and Na+ pump activity were estimated by in vivo 31p and 23Na nuclear magnetic resonance (NMR) spectroscopy, and CBF was determined by [14C]iodoantipyrine methods at the end of the experiments. The CBF measured in normotensive animals was 0.51 ± 0.07 ml/g brain/min. Following graded hypotension, no 31P spectral change was observed until CBF fell to 0.21–0.27 ml/g brain/min, at which level the intracellular pH began to decrease in association with ECoG voltage reduction. At a CBF level of 0.18–0.23 ml/g brain/min, phosphocreatine (PCr) began to decrease in association with inorganic phosphate (Pi) elevation. At this level, ECoG became isoelectric, although no adenosine triphosphate (ATP) change yet resulted. At a flow level of 0.12–0.14 ml/g brain/min, ATP began to decrease gradually. At 0.04–0.05 ml/g brain/min, PCr and ATP virtually disappeared, and the 23Na signal intensity suddenly changed. The present study demonstrated flow thresholds for the development of tissue acidosis, PCr–Pi changes, and ATP reduction. It appears that functional suppression occurs prior to ATP changes, whereas Na+ pump failure results after ATP depletion.

scholarly journals Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action

1997 ◽  
Vol 83 (3) ◽  
pp. 867-874 ◽  
Author(s):  
T. W. Ryschon ◽  
M. D. Fowler ◽  
R. E. Wysong ◽  
A.-R. Anthony ◽  
R. S. Balaban
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Production Rate ◽  
Human Skeletal Muscle ◽  
Atp Synthesis ◽  
High Energy ◽  
High Energy Phosphates ◽  
Muscle Action ◽  
Atp Production

Ryschon, T. W., Fowler, R. E. Wysong, A.-R. Anthony, and R. S. Balaban. Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action. J. Appl. Physiol. 83(3): 867–874, 1997.—The purpose of this study was to estimate the efficiency of ATP utilization for concentric, eccentric, and isometric muscle action in the human tibialis anterior and extensor digitorum longus in vivo. A dynamometer was used to quantitate muscle work, or tension, while simultaneous 31P-nuclear magnetic resonance data were collected to monitor ATP, phosphocreatine, inorganic phosphate, and pH. The relative efficiency of the actions was estimated in two ways: steady-state effects on high-energy phosphates and a direct comparison of ATP synthesis rates with work. In the steady state, the cytosolic free energy dropped to the lowest value with concentric activity, followed by eccentric and isometric action for comparative muscle tensions. Estimates of ATP synthesis rates revealed a mechanochemical efficiency [i.e., ATP production rate/work (both in J/s)] of 15.0 ± 1.3% in concentric and 34.7 ± 6.1% in eccentric activity. The estimated maximum ATP production rate was highest in concentric action, suggesting an activation of energy metabolism under these conditions. By using direct measures of metabolic strain and ATP turnover, these data demonstrate a decreasing metabolic efficiency in human muscle action from isometric, to eccentric, to concentric action.

scholarly journals The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes

1976 ◽  
Vol 154 (2) ◽  
pp. 449-469 ◽  
Author(s):  
T A. Rapoport ◽  
R Heinrich ◽  
S M. Rapoport
Keyword(s):  
Steady State ◽  
Atp Synthesis ◽  
Steady States ◽  
Time Dependent ◽  
Glycolytic Flux ◽  
Stable Steady State ◽  
Time Interval ◽  
Fructose 1,6 Bisphosphate

A simple mathematical model for glycolysis in erythrocytes is presented which takes into account ATP synthesis and consumption. The system is described by four ordinary differential equations. Conditions in vivo are described by a stable steady state. The model predicts correctly the metabolite concentrations found in vivo. The parameters involved are in agreement with data on the separate steps. The metabolite changes found in pyruvate kinase-deficient erythrocytes and the species variations among erythrocytes from different animals are described satisfactorily. The roles of the enzymes in the control of metabolites and glycolytic flux are expressed in the form of a control matrix and control strengths [R. Heinrich & T.A. Rapoport (1974) Eur. J. Biochem. 42, 89-95] respectively. Erythrocytes from various species are shown to be adapted to a maximal ATP-consumption rate. The calculated eigenvalues reveal the pronounced time-hierarchy of the glycolytic reactions. Owing to the slowness of the 2,3-bisphospho-glycerate phosphatase reaction, quasi-steady states occur during the time-interval of about 0.5-2h incubation, which are defined by perturbed 2,3-bisphosphoglycerate concentrations. The theoretical predictions agree with experimental data. In the quasi-steady state the flux control is exerted almost entirely by the hexokinase-phosphofructokinase system. The model describes satisfactorily the time-dependent changes after addition of glucose to starved erythrocytes. The theoretical consequences are discussed of the conditions in vitro with lactate accumulation and the existence of a time-independent conservation quantity for the oxidized metabolites. Even in this closed system quasi-steady states occur which are characterized by approximately constant concentrations of all glycolytic metabolites except for the accumulation of lactate, fructose 1,6-bisphosphate and triose phosphate.

scholarly journals Effect of Bacterial Endotoxins on Superovulated Mouse Embryos In Vivo: Is CSF-1 Involved in Endotoxin-Induced Pregnancy Loss?

2006 ◽  
Vol 2006 ◽  
pp. 1-9 ◽  
Author(s):  
Yogesh Kumar Jaiswal ◽  
Madan Mohan Chaturvedi ◽  
Kaushik Deb
Keyword(s):  
Embryonic Development ◽  
Pregnancy Loss ◽  
Mouse Embryos ◽  
Preimplantation Embryos ◽  
Implantation Failure ◽  
Normal Pattern ◽  
Bacterial Endotoxins ◽  
Mammalian Embryonic Development ◽  
Lps Treatment

Mammalian embryonic development is regulated by several cytokines and growth factors from embryonic or maternal origins. Since CSF-1 plays important role in embryonic development and implantation, we investigated its role in gram-negative bacterial LPS-induced implantation failure. The effect of LPS on normal (nonsuperovulated) and superovulated in vivo-produced embryos was assessed by signs of morphological degeneration. A significantly similar number of morphologically degenerated embryos recovered from both nonsuperovulated and superovulated LPS treated animals on day 2.5 of pregnancy onwards were morphologically and developmentally abnormal as compared to their respective controls (P<.001. Normal CSF-1 expression level and pattern were also altered through the preimplantation period in the mouse embryos and uterine horns after LPS treatment. This deviation from the normal pattern and level of CSF-1 expression in the preimplantation embryos and uterine tissues suggest a role for CSF-1 in LPS-induced implantation failure.

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