Increased hypoxic stress decreases AMP hydrolysis in rabbit heart

Gustafson, Lori A.; Zuurbier, Coert J.; Bassett, John Spencer; Barends, J. P. F.; Beek, Hans van; Bassingthwaighte, James B.; Kroll, Keith

doi:10.1016/s0008-6363(99)00207-2

Cited by 15 publications

(6 citation statements)

References 29 publications

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“…This agrees with a study on AMPD in muscle of hibernating mammals that found that substrate affinity was reduced at low temperatures in the torpid state [ 16 ]. AMPD was also inhibited in rabbit heart experiencing hypoxia [ 34 ]. In that study, AMP deamination was high early in the ischemic period, and this served to preserve the AEC.…”

Section: Discussionmentioning

confidence: 99%

Regulation of 5'-adenosine monophosphate deaminase in the freeze tolerant wood frog, Rana sylvatica

Dieni

Storey

2008

BMC Biochemistry

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BackgroundThe wood frog, Rana sylvatica, is one of a few vertebrate species that have developed natural freeze tolerance, surviving days or weeks with 65–70% of its total body water frozen in extracellular ice masses. Frozen frogs exhibit no vital signs and their organs must endure multiple stresses, particularly long term anoxia and ischemia. Maintenance of cellular energy supply is critical to viability in the frozen state and in skeletal muscle, AMP deaminase (AMPD) plays a key role in stabilizing cellular energetics. The present study investigated AMPD control in wood frog muscle.ResultsWood frog AMPD was subject to multiple regulatory controls: binding to subcellular structures, protein phosphorylation, and effects of allosteric effectors, cryoprotectants and temperature. The percentage of bound AMPD activity increased from 20 to 35% with the transition to the frozen state. Bound AMPD showed altered kinetic parameters compared with the free enzyme (S0.5 AMP was reduced, Hill coefficient fell to ~1.0) and the transition to the frozen state led to a 3-fold increase in S0.5 AMP of the bound enzyme. AMPD was a target of protein phosphorylation. Bound AMPD from control frogs proved to be a low phosphate form with a low S0.5 AMP and was phosphorylated in incubations that stimulated PKA, PKC, CaMK, or AMPK. Bound AMPD from frozen frogs was a high phosphate form with a high S0.5 AMP that was reduced under incubation conditions that stimulated protein phosphatases. Frog muscle AMPD was activated by Mg·ATP and Mg·ADP and inhibited by Mg·GTP, KCl, NaCl and NH4Cl. The enzyme product, IMP, uniquely inhibited only the bound (phosphorylated) enzyme from muscle of frozen frogs. Activators and inhibitors differentially affected the free versus bound enzyme. S0.5 AMP of bound AMPD was also differentially affected by high versus low assay temperature (25 vs 5°C) and by the presence/absence of the natural cryoprotectant (250 mM glucose) that accumulates during freezing.ConclusionMaintenance of long term viability under the ischemic conditions in frozen muscle requires attention to the control of cellular energetics. Differential regulatory controls on AMPD by mechanisms including binding to muscle proteins, actions allosteric effectors, glucose and temperature effects and reversible phosphorylation adjust enzyme function for an optimal role in controlling cellular adenylate levels in ischemic frozen muscle. Stable modification of AMPD properties via freeze-responsive phosphorylation may contribute both to AMPD control and to coordinating AMPD function with other enzymes of energy metabolism in cold ischemic muscle.

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Section: Discussionmentioning

confidence: 99%

Regulation of 5'-adenosine monophosphate deaminase in the freeze tolerant wood frog, Rana sylvatica

Dieni

Storey

2008

BMC Biochemistry

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“…The concentration of AMP is another factor influencing the degradation of nucleotides. Its conversion to adenosine by cytosolic 5′‐nucleotidase (5NT) or to IMP by AMP deaminase determines the degree of nucleotide degradation and ATP resynthesis during reoxygenation 38. In the deeply hypothermic rat, the accumulation of brain AMP during asphyxia begins with a conspicuous lag (Fig.…”

Section: Discussionmentioning

confidence: 99%

Brain Energetics and Tolerance to Anoxia in Deep Hypothermia

Andjus¹,

Džakula²,

Markley³

et al. 2005

Annals of the New York Academy of Sciences

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The remarkable time-resolution enhancement by deep lethargic hypothermia (15 degrees C rectal temperature, "cold narcosis," "anesthesia by internal cold") of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo (31)P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.

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“…MgADP might be degraded further (Allen et al 1985) by the myokinase reaction. The calculation of [MgADP] i during ischaemia is not straightforward (Ingwall, 1987) because creatine kinase (Ventura‐Clapier & Veksler, 1994), myokinase (Golding et al 1995) and other enzymes involved in the catabolic processes (Gustafson et al 1999) are all sensitive to ischaemic metabolites. Recent data on intact skeletal muscle fibres suggest that [MgADP] i may reach levels high enough to induce marked alterations in cross‐bridge kinetics (Westerblad et al 1998).…”

Section: Discussionmentioning

confidence: 99%

The mechanism of the force enhancement by mgADP under simulated isChaemic conditions in rat cardiac myocytes

Papp

Szabó

Barends

et al. 2002

The Journal of Physiology

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The interpretation of skinned fibre experiments in the presence of MgADP and the absence of CP is complicated by intracellular adenine nucleotide gradients caused by ATP hydrolysis and diffusion of the reactants (e.g. Cooke & Pate, 1985). In order to minimize the intracellular concentration gradients, isolated Triton-permeabilized myocytes were used in this study. In addition, model calculations were employed to evaluate the influence of the adenine nucleotide concentration profiles inside the cardiomyocytes.

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Increased hypoxic stress decreases AMP hydrolysis in rabbit heart

Cited by 15 publications

References 29 publications

Regulation of 5'-adenosine monophosphate deaminase in the freeze tolerant wood frog, Rana sylvatica

Regulation of 5'-adenosine monophosphate deaminase in the freeze tolerant wood frog, Rana sylvatica

Brain Energetics and Tolerance to Anoxia in Deep Hypothermia

The mechanism of the force enhancement by mgADP under simulated isChaemic conditions in rat cardiac myocytes

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