The effect of anaerobiosis on adenosine nucleotide levels inNematospiroides dubiusandTrichostrongylus colubriformis in vitro

Parasitology ◽  
1981 ◽  
Vol 83 (2) ◽  
pp. 425-433 ◽  
Author(s):  
M. J. Sharpe ◽  
D. L. Lee
Keyword(s):  
Adverse Effect ◽  
Energy Charge ◽  
Adenylate Energy Charge ◽  
Anoxic Conditions ◽  
Adenylate Pool ◽  
Nematospiroides Dubius ◽  
Adenosine Nucleotide ◽  
Sufficient Oxygen

SUMMARYThe adenosine nucleotide and adenylate energy charge values ofNematospiroides dubiusandTrichostrongylus colubriformismaintainedin vitrounder aerated and under near-anoxic conditions have been measured. Maintenance of the nematodes in both conditions had an adverse effect on their energy metabolism, but in comparing these effects it was found that the changes were more significant in those nematodes maintained in near-anoxic conditions and that the changes were more apparent in male nematodes. The smaller changes in the energy charge values of female worms, particularlyN. dubiuswhere there was no difference between worms in aerated conditions and those in near-anoxic conditions, were explained by the presence of eggs in the nematodes. At no time did the energy charge of nematodes in near-anoxic conditions fall below 0·50 but, whereas nematodes in aerated conditions were able to continue moving throughout the experiment, those in near-anoxic conditions stopped moving during the first 3 h. It is suggested that in the absence of sufficient oxygen the nematodes were able to maintain their energy charge above 0·50 by removal of AMP from the adenylate pool, resulting in the depletion of their total adenylate. The changes in the energy charge and behaviour of the nematodes are related to the survival of the nematodes in the oxygen-deficient environment which they inhabitin vivo.

Control of AMP deaminase 1 binding to myosin heavy chain

1998 ◽  
Vol 275 (3) ◽  
pp. C870-C881 ◽  
Author(s):  
Ichiro Hisatome ◽  
Takayuki Morisaki ◽  
Hiroshi Kamma ◽  
Takako Sugama ◽  
Hiroko Morisaki ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Sequence Similarity ◽  
Critical Role ◽  
Energy Charge ◽  
Adenylate Energy Charge ◽  
Amp Deaminase ◽  
Amino Terminal

AMP deaminase (AMPD) plays a central role in preserving the adenylate energy charge in myocytes following exercise and in producing intermediates for the citric acid cycle in muscle. Prior studies have demonstrated that AMPD1 binds to myosin heavy chain (MHC) in vitro; binding to the myofibril varies with the state of muscle contraction in vivo, and binding of AMPD1 to MHC is required for activation of this enzyme in myocytes. The present study has identified three domains in AMPD1 that influence binding of this enzyme to MHC using a cotransfection model that permits assessment of mutations introduced into the AMPD1 peptide. One domain that encompasses residues 178–333 of this 727-amino acid peptide is essential for binding of AMPD1 to MHC. This region of AMPD1 shares sequence similarity with several regions of titin, another MHC binding protein. Two additional domains regulate binding of this peptide to MHC in response to intracellular and extracellular signals. A nucleotide binding site, which is located at residues 660–674, controls binding of AMPD1 to MHC in response to changes in intracellular ATP concentration. Deletion analyses demonstrate that the amino-terminal 65 residues of AMPD1 play a critical role in modulating the sensitivity to ATP-induced inhibition of MHC binding. Alternative splicing of the AMPD1 gene product, which alters the sequence of residues 8–12, produces two AMPD1 isoforms that exhibit different MHC binding properties in the presence of ATP. These findings are discussed in the context of the various roles proposed for AMPD in energy production in the myocyte.

Changes in the adenylate energy charge ofNematospiroides dubiusandTrichostrongylus colubriformisparalysed by levamisolein vivo

Parasitology ◽  
1980 ◽  
Vol 81 (3) ◽  
pp. 593-601 ◽  
Author(s):  
M. J. Sharpe
Keyword(s):  
Oxygen Tension ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Adenylate Energy Charge ◽  
Laboratory Mice ◽  
Trichostrongylus Colubriformis ◽  
Nucleotide Content ◽  
Nematospiroides Dubius ◽  
Low Levels

SUMMARYThe adenine nucleotide content and adenylate energy charge ofNematospiroides dubiusfrom laboratory mice and ofTrichostrongylus colubriformisfrom lambs has been measured. Administration of the anthelmintic, levamisole, to infected hosts resulted in only a slight fall in the adenylate energy charge ofN. dubiusover a 3-h period but there was a greater fall in the adenylate energy charge ofT. colubriformisduring this period. In neither case did the energy charge fall quickly, nor did it fall to the low levels which would be expected if the levamisole were inhibiting synthesis of ATP. The changes in energy charge of the nematodes which occurred following administration of levamisole to their hosts was of the order which can be satisfactorily explained by changes in the environment of the nematodes, such as reduced oxygen tension. It is concluded that the maintenance of levamisole-induced paralysis of these two species of trichostrongylein vivodoes not rely on the inhibition of fumarate reductase.

scholarly journals Lactic Acidosis and Recovery of Mitochondrial Function following Forebrain Ischemia in the Rat

1985 ◽  
Vol 5 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Lars Hillered ◽  
Maj-Lis Smith ◽  
Bo K. Siesjö
Keyword(s):  
Lactic Acidosis ◽  
Mitochondrial Function ◽  
Respiratory Activity ◽  
Energy Charge ◽  
Complete Recovery ◽  
Adenylate Energy Charge ◽  
Forebrain Ischemia ◽  
Early Recovery

The effect of different degrees of lactic acidosis on the recovery of brain mitochondrial function, measured as respiratory activity in isolated mitochondria or cortical concentrations of labile phosphates and carbohydrate substrates, was studied during 30 min of recirculation following 15 min of near-complete forebrain ischemia in rats. During ischemia, there was a marked decrease in mitochondrial State 3 respiration in vitro and a depletion of energy stores (i.e., phosphocreatine, ATP, glucose, and glycogen) in vivo that was similar in the high- and low-lactate ischemia groups. However, lactate concentrations differed markedly (20 and 10 μmol g−1, respectively). During recirculation, there was a near-complete recovery of both respiratory activity in vitro and adenylate energy charge (EC) in vivo regardless of the differences in lactic acidosis during ischemia. Respiratory activity and EC were well correlated. The changes in Ca2+ homeostasis during ischemia, an increase in tissue and a decrease in mitochondrial Ca2+ content, were reversed rapidly after ischemia in both high- and low-lactate ischemia animals and did not hinder an early recovery of mitochondrial function. It is concluded that lactic acidosis, with lactate levels reaching 20 μmol g−1 during 15-min ischemia, does not adversely affect early postischemic recovery of mitochondrial function.

scholarly journals A MICROCALORIMETRIC STUDY OF TURTLE CORTICAL SLICES: INSIGHTS INTO BRAIN METABOLIC DEPRESSION

1994 ◽  
Vol 191 (1) ◽  
pp. 141-153 ◽  
Author(s):  
C Doll ◽  
P Hochachka ◽  
S Hand
Keyword(s):  
Cortical Neurons ◽  
Heat Dissipation ◽  
Energy Charge ◽  
Utilization Rate ◽  
Rapid Decline ◽  
Metabolic Depression ◽  
Slice Preparation ◽  
Cortical Slices

In previous papers, we have examined turtle cortical neurons in vitro for mechanisms of anoxic metabolic depression ('channel arrest' and changes in electrical parameters). Negative results prompted the current study with the aim of examining more closely the energy profile and metabolism of turtle cortical slices. Calorimetry is used to measure heat dissipation during normoxia and nitrogen perfusion (120 min) and the results are converted into an ATP utilization rate. These indicate that the control rate of ATP utilization (1.72 µmol ATP g-1 min-1) agrees closely with in vivo whole-brain metabolic measurements. Both nitrogen perfusion and pharmacologically induced anoxic (cyanide+N2) groups depressed heat dissipation considerably compared with the control value (nitrogen 37 %; pharmacological anoxia 49 %). The resulting ATP utilization estimates indicate metabolic depressions of 30 % (nitrogen) and 42 % (pharmacological anoxia). The slice preparation did not exhibit a change in any measured adenylate parameter for up to 120 min of anoxia or pharmacological anoxia. Significant changes did occur in [ADP], ATP/ADP ratio and energy charge after 240 min of exposure to anoxic conditions. These results support the idea that the turtle cortical slice preparation has a profound resistance to anoxia, with both nitrogen perfusion and pharmacological anoxia causing a rapid decline in heat dissipation and metabolism.

DEVELOPMENT, CHARACTERIZATION AND BRAIN DISTRIBUTION STUDIES OF NANOSTRUCTURED LIPID CARRIER CONTAINING SAQUINAVIR MESYLATE FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (09) ◽  
pp. 38-47
Author(s):  
H. S. Mahajan ◽  
◽  
M. I. Patel
Keyword(s):  
Adverse Effect ◽  
Targeted Delivery ◽  
Entrapment Efficiency ◽  
Nasal Administration ◽  
Nanostructured Lipid Carrier ◽  
Brain Distribution ◽  
Scanning Calorimetry ◽  
Distribution Studies

The aim of the present study was to formulate saquinavir mesylate loaded nanostructured lipid carriers (SQVM-NLC) and evaluate its brain distribution after nasal administration. NLCs reveal some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. SQVM-NLCs were prepared by hot high pressure homogenization and subsequent stabilization by lyophilization. QVM- NLC developed showed a particle with the size of 124.4 nm, polydispersity index of 0.267, entrapment efficiency of 73% and the zeta potential of -24.9 mV. The results from Scanning Electron Microscopy (SEM), powder X-ray diffraction (XRD)and differential scanning calorimetry (DSC) demonstrated that SQVM was present in NLC in an encapsulated molecule form. Mucosal toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVMloaded NLC. SQVM-NLC showed slower release compared with saquinavir mesylate suspension in vitro. In vivo brain distribution studies demonstrated desired drug concentration in brain after intra nasal administration of SQVM-NLC than PDS. The results of the study also suggest that SQVM-NLC could be a promising drug delivery system for antiretroviral therapy.

scholarly journals Labeling of the releasable adenine nucleotides of washed human platelets

Blood ◽  
1977 ◽  
Vol 49 (1) ◽  
pp. 89-99 ◽  
Author(s):  
HJ Reimers ◽  
MA Packham ◽  
JF Mustard
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
Human Platelets ◽  
Transport Processes ◽  
Adenylate Energy Charge ◽  
Prolonged Incubation ◽  
Atp Pool ◽  
Adenine Nucleotide Pool

Abstract In rabbit platelets, the metabolically active ATP pool equilibrates with the releasable ATP pool within 1 day. The studies showing this have now been extended to human platelets. Human platelets labeled with 14C-adenosine or 14C-adenine were incubated for up to 10 hr in vitro at 37 degrees C. After 10 hr, about 12% of the total platelet 14C-ATP and 14C-ADP had become releasable with thrombin (4.2 units/ml). Lysis of platelets did not occur, since less than 1% of the platelet-bound 51Cr from platelets labeled with this radioisotope appeared in the ambient fluid upon thrombin treatment. The 14C-ATP/14C-ADP ratio of the released adenine nucleotides (7.6) was similar to the 14C-ATP/14C-ADP ratio of the nonreleasable adenine nucleotides (7.1) 2 hr after the labeling with 14C-adenosine. However, upon prolonged incubation (10 hr) in vitro, the 14C-ATP/14C-ADP ratio of the releasable adenine nucleotides decreased to 2.7. The adenylate energy charge and the 14C- ATP/14C-ADP ratio of the metabolic adenine nucleotide pool did not change significantly during the time of observation. The 14C-ATP content of the platelets decreased by less than 1% hr of incubation at 37 degrees C. These observations are interpreted to mean that the 14C is transferred from the metabolically active, nonreleasable adenine nucleotide pool of human platelets into the releasable adenine nucleotide pool as ATP and is partially hydrolyzed there to yield ADP. The transfer of ATP across the storage organelle membrane of platelets may be similar to transport processes in the chromaffin cells of the adrenal medulla and may represent a general phenomenon in cells that possess storage organelles containing adenine nucleotides.

Adverse Effect of Heparin on Thrombin Inactivation

1975 ◽  
Author(s):  
E. Marciniak
Keyword(s):  
Adverse Effect ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Binding Properties ◽  
Inhibitory Capacity ◽  
Antithrombin Iii Deficiency ◽  
Final Amount ◽  
Native Plasma

In the presence of heparin thrombin, although fast inactivated, impairs the inhibitory capacity of antithrombin III, in result of which the final amount of neutralized enzyme markedly decreases. This adverse effect of heparin was found during the reaction of purified thrombin with both purified human antithrombin III and native plasma hepariniz purified thrombin with both purified human antithrombin III and native plasma heparinized in vitro or in vivo. In the absence of heparin, at concentration equal to that in normal plasma antithrombin III binds 450 Iowa units of thrombin; in the presence of heparin (at 1 unit concentration) this binding is reduced to 145 thrombin units. A fast depletion of inhibitory capacity is also evident after a stepwise addition of thrombin in small installments into a medium containing antithrombin III and heparin. Portions of enzyme initially added disappear with great velocity; subsequent additions, however, accumulate building up a high thrombin level not seen in the absence of heparin. The escalation of thrombin is reversely proportional to the reacting antithrombin III level, thus especially noticeable in antithrombin III deficient plasma. Residual thrombin left in the presence of heparin disappears at a fast rate upon a new addition of antithrombin III. No decrease in anticoagulant properties of heparin is observed during these interactions. Binding of factor Xa to antithrombin III which reacted with thrombin and heparin is also decreased or abolished.These results indicate that in the presence of heparin thrombin not only exposes rapidly a binding site on the inhibitor, but also causes a further change leading to the deletion of antithrombin III binding properties. This may explain adverse, thrombotic effect of heparin sporadically seen in vivo, and suggests that heparin should be applied with caution in patients with antithrombin III deficiency.

Reproductive Behavior of Nematospiroides dubius In vivo and In vitro

1964 ◽  
Vol 50 (3) ◽  
pp. 401 ◽  
Author(s):  
R. I. Sommerville ◽  
Paul P. Weinstein
Keyword(s):  
Reproductive Behavior ◽  
Nematospiroides Dubius

The influence of oxygen on the radiosensitizing activity of Photofrin II and hypericin

2007 ◽  
Vol 11 (10) ◽  
pp. 736-741 ◽  
Author(s):  
Pamela Schaffer ◽  
Ulrike Kulka ◽  
Birgit Ertl-Wagner ◽  
Roswita Hell ◽  
Alina Balandin ◽  
...  
Keyword(s):  
Carcinoma Cell ◽  
Cell Damage ◽  
Human Bladder ◽  
Photofrin Ii ◽  
Carcinoma Cell Lines ◽  
Radiation Induced ◽  
Low Levels ◽  
Sufficient Oxygen

Several clinical studies, as well as investigations performed on tissue cultures and murine tumor models, have demonstrated the in vitro and in vivo efficacy of Photofrin II and hypericin as radiosensitizing agents. The mechanisms involved in the radiosensitizing action of Photofrin II and hypericin are partially understood; the recognition of the major role performed by oxygen regarding the modulation of cellular radiosensitivity has prompted the present investigations on the relevance of oxygenation for the success of Photofrin II or hypericin-based radiation therapy of tumors. RT4 human bladder carcinoma cell lines were seeded and incubated with various concentrations of Photofrin II or hypericin under ambient and 5% oxygen levels. The cells were irradiated with ionizing radiation between 1 and 6 Gy. The same experiments were repeated with Photofrin II and hypericin alone, without radiation. The cell survival was evaluated. The results demonstrated an increase of radiation-induced cell damage in the presence of Photofrin II and hypericin, respectively, when sufficient oxygen was available. Low levels of oxygen reduced the activity of Photofrin II as well as of hypericin as a radiosensitizer, with minimal tumor damage ( p < 0.05 in a Student t-test). The mechanism of action of Photofrin II and hypericin as radiosensitizers requires the presence of sufficiently high oxygen concentrations.

scholarly journals Signal-transduction protein PII from Synechococcus elongatus PCC 7942 senses low adenylate energy charge in vitro

2011 ◽  
Vol 440 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Oleksandra Fokina ◽  
Christina Herrmann ◽  
Karl Forchhammer
Keyword(s):  
Signal Transduction ◽  
Energy Charge ◽  
Inhibitory Effect ◽  
Synechococcus Elongatus ◽  
Adenylate Energy Charge ◽  
Signal Transduction Protein ◽  
Signal Transduction Proteins ◽  
Synechococcus Elongatus Pcc 7942 ◽  
And Control

PII proteins belong to a family of highly conserved signal-transduction proteins that occurs widely in bacteria, archaea and plants. They respond to the central metabolites ATP, ADP and 2-OG (2-oxoglutarate), and control enzymes, transcription factors and transport proteins involved in nitrogen metabolism. In the present study, we examined the effect of ADP on in vitro PII-signalling properties for the cyanobacterium Synechococcus elongatus, a model for oxygenic phototrophic organisms. Different ADP/ATP ratios strongly affected the properties of PII signalling. Increasing ADP antagonized the binding of 2-OG and directly affected the interactions of PII with its target proteins. The resulting PII-signalling properties indicate that, in mixtures of ADP and ATP, PII trimers are occupied by mixtures of adenylate nucleotides. Binding and kinetic activation of NAGK (N-acetyl-L-glutamate kinase), the controlling enzyme of arginine biosynthesis, by PII was weakened by ADP, but relief from arginine inhibition remained unaffected. On the other hand, ADP enhanced the binding of PII to PipX, a co-activator of the transcription factor NtcA and, furthermore, antagonized the inhibitory effect of 2-OG on PII–PipX interaction. These results indicate that S. elongatus PII directly senses the adenylate energy charge, resulting in target-dependent differential modification of the PII-signalling properties.

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