Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle has been investigated using the needle biopsy technique. Preliminary studies showed that the activity of phosphorylase in vitro was dependent upon the concentration of inorganic phosphate (Pi) used in the assay system. The Km of phosphorylase a for Pi was found to be 26.2 mmol/l, and that of (a+b) (assayed in the presence of saturating AMP) was 6.8 mmol/l. Because of the difference in Km the apparent percentage of a to (a+b) activity varies with the Pi concentration used in the assay system. Phosphorylase a and (a+b) activities were therefore adjusted to saturating Pi concentrations. The ratio of the activities in this case is independent of the Pi concentration and constitutes a minimal estimate of the fraction of phosphorylase molecules in the a form. The fraction of phosphorylase in the a form in resting muscle was as a mean 22%. Despite nearly a quarter of the phosphorylase being in the a form glycogenolytic activity is extremely low. It is proposed that the concentration of Pi at the active site of the enzyme is low compared to the Km for this of either form of the enzyme, and is limiting to activity. A Pi concentration in resting muscle of 1-3 mmol/l was calculated. During epinephrine infusion at rest 90% of the phosphorylase was transformed to the a form but only a moderate increase in the glycogenolytic rate occurred. This rate approximated to 5-10% of the maximum rate of the enzyme (Vmaxa). During prolonged epinephrine infusion the glycogenolytic rate decreased despite the continuance of 90% or more of the phosphorylase in the a form. In contrast to epinephrine infusion prolonged ischemia resulted in a decrease in the mole fraction of phosphorylase a and simultaneously in an increase of the glycogenolytic rate. During isometric and dynamic exercise there was a rapid transformation of phosphorylase b to a paralleled by pronounced increase in the rate of glycogen breakdown. The increased rate of glycogenolysis during isometric exercise was close to the Vmax of phosphorylase a in vivo. When either form of exercise was continued to fatigue/exhaustion, a re-transformation of phosphorylase a to b was observed. During dynamic exercise cAMP in the muscle increased two fold. This increase was blocked by the prior administration of propranolol.+
 ...
PMID:The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle. 613 34

Effect of short-term partial limitation of coronary circulation (by 30%, 50% and 70%) on energy formation in myocardium was studied in animals with closed thorax after catheterization and autoperfusion of the circumflex branch of left coronary artery. Distinct alterations in energy metabolism were observed already after a decrease of the coronary circulation by 30%. Several enzymes were inhibited in tricarboxylic acid cycle and in respiratory chain following development of ischemia. Despite of the inhibition of the aerobic oxidation content of ATP and glycogen maintained rather stable. Content of ATP was decreased down to 60% of the initial level only after limitation of the circulation by 2/3. Deficiency in aerobic energy production as well as maintaining of a rather stable content of ATP and glycogen were apparently compensated by an increase in cAMP content, activation of glycolysis and pentose phosphate pathway and of adenosine formation.
 ...
PMID:[Energy formation processes in the myocardium during measured limitation of coronary blood flow]. 625 21

The effect of prostacyclin (PGI2, 0.5 nmol . kg-1 . min-1,i.v.) on myocardial metabolism was studied in cats subjected to 5 h of myocardial ischemia (MI) and compared to vehicle-treated MI cats. MI was followed by a 52% decrease in ATP and a concomitant increase (2-3 fold) in lactate and lactate/pyruvate ratio in the severely ischemic area. PGI2 prevented this increase in lactate with an unchanged ATP and lactate/pyruvate ratio. Moreover, PGI2 abolished the ischemia-induced in myocardial cAMP. It is concluded, the PGI2 exerts its beneficial actions on ischemic myocardium partly via cAMP-linked mechanisms.
 ...
PMID:Prostacyclin prevents ischemia-induced increase of lactate and cyclic AMP in ischemic myocardium. 626 30

Dosaged restriction of coronary blood flow (by 30, 50, 70 and 90%) was reproduced for 30 minutes in dogs with a closed chest. In all degrees of coronary blood flow restriction the loss of glycogen, accumulation of lactic acid and cAMP (in reduction of blood flow by 50 and 70%) and activation of glycogenolysis, phosphorylase and phosphofructokinase were recorded in the zone of ischemia. The changes advanced with the deepening of ischemia. Similar, though less pronounced changes were found outside the ischemic zone. Marked metabolic shifts were disclosed in the right ventricle. The mechanisms of anaerobic oxidation activation in ischemia are discussed.
 ...
PMID:[Myocardial carbohydrate metabolism in limited coronary blood flow]. 626 47

The incubation of adult mouse skin pieces in a buffered salts medium at 37 degrees C led to a rapid accumulation of cyclic adenosine 3'5-monophosphate (cyclic AMP) in the tissue. In mouse skin maximum accumulation occurred after 2 min incubation; levels reverted to near control levels after a further 7 min incubation. the increase in cyclic AMP contents of the skin pieces was probably not due to the release of materials which activate adenylate cyclase after binding to cellular receptors. Thus, cyclic AMP accumulation was unaffected by the inclusion of alpha- or beta-adrenergic antagonists, or by the pretreatment of adult mouse skin with indomethacin (an inhibitor of prostaglandin synthetase). Furthermore, adenosine, a known activator of epidermal adenylate cyclase, could not be detected in the incubation medium. The functional integrity of epidermal adenylate cyclase was maintained during the cyclic AMP accumulation in response to ischemia. Thus, adenosine, histamine, isoproterenol and prostaglandin E2 (PGE2) augmented the cyclic AMP response. Cyclic AMP accumulation at 37 degrees C was not observed in newborn mouse skin; this lack of cyclic AMP accumulation was probably not due to increased activity of low affinity cyclic AMP phosphodiesterase in newborn mouse skin.
 ...
PMID:The effect of ischemia on cyclic adenosine 3',5'monophosphate accumulation in mouse skin. 627 64

Cyclic AMP-dependent protein kinase isozymes of pig and human skin (epidermis) were separated by DEAE-cellulose column chromatography after micromodification for small biopsy samples. Clear-cut separations of type I and type II isozymes, which were of about equal amounts, could be obtained only when the ischemia effect was avoided by in vivo freezing of skin and homogenization for less than 10 s. Intradermal injections of epinephrine caused dose-dependent activation of type I isozyme, but not of type II. Injections of other skin adenylate cyclase stimulators such as histamine, adenosine, and prostaglandin E2 elevated the local cyclic AMP levels to not more than 5 pmol/mg protein and also stimulated only the type I isozyme. Incubation of keratome-sliced pig skin under various conditions caused both activation by dissociation and inactivation by reassociation of the subunits, which appeared to be dependent on the cyclic AMP content. Epinephrine added to the incubation medium led to complete activation of both type I and type II isozymes (the intraepidermal cyclic AMP contents ranged from 20-50 pmol/mg protein). The isozymes of normal skin and involved skin of psoriatics showed identical peaks of type I and type II isozymes of equal amounts. The data indicate that protein kinase in the involved skin is not in an activated (by cyclic AMP) state.
 ...
PMID:Cyclic AMP-dependent protein kinase isozymes of pig skin and human skin from normal and psoriatic subjects. 629 36

Following coronary artery ligation (CAL), levels of cAMP and the activity ratio of cAMP-dependent protein kinase, of phosphorylase kinase, and of phosphorylase are significantly elevated in both ischemic and nonischemic areas of the canine left ventricle. The aerobic level of cAMP was found to be 0.4 to 0.6 pmol/mg myocardium only after a precooled clamp or a cryobiopsy device was employed to guarantee tissue freezing in situ. Maximal changes in response to ischemia are observed within 2 min in both parts of the heart. Twenty minutes after the onset of ischemia, different responses have been found in the nonischemic and ischemic tissue. Whereas the levels of cAMP and the activity ratio of protein kinase, of phosphorylase kinase, and of phosphorylase returned to aerobic values in the nonischemic area, these parameters remained elevated in the ischemic area. The changes in the levels of myocardial cAMP and in the cAMP-dependent protein kinase activity ratio following CAL could be prevented by propranolol.
 ...
PMID:Cyclic nucleotides and changes in protein kinase activity ratio in the ischemic and nonischemic myocardium. 630 32

Using specially modified automatic freeze clamps studies were undertaken to determine the importance of rapid freeze clamping in the determination of myocardial cAMP content. Modification of the freeze clamps allowed the separation of the physical processes of clamping and freezing. When the tissue was clamped and maintained at 37 degrees C for periods in excess of 5 s before freezing cyclic AMP content increased by up to 100%. When clamped and held at room temperature (20 degrees C) increase were again observed if the freezing delay exceeded 5 s, however, the increases were not as great as those observed with 37 degrees C clamping. The biphasic time-dependency curve for tissue cAMP content v. clamping delay bears a close similarity to that observed following the onset of tissue ischemia suggesting perhaps that ischemia, secondary to mechanical clamping, rather than sympathetic stimulation, is the cause of the rise. It can be concluded that for reliable measurements of cAMP content tissue should be frozen within less than 5 s of sampling.
 ...
PMID:Myocardial cyclic AMP determinations: the importance of rapidity of sample freezing. 631 58

In 12 healthy, adult males, the epidermal content of both cAMP and cGMP was determined radioimmunologically every 6 h over a period of 30 h, avoiding any ischemia, which can alter unphysiologically the in vivo levels of epidermal cyclic nucleotides. For cAMP a diurnal fluctuation with maximal level at midnight could be proved (p less than 0.05), whereas cGMP, in contrast to experiments in mice, revealed no significant variation during the test period. The presented results describe for the first time the diurnal course of human epidermal cGMP.
 ...
PMID:Cyclic nucleotides in human epidermis--diurnal variations. 631

The transverse guinea pig hippocampal slice preparation was used to model the metabolic changes which occur in vivo during ischemia and recovery. Perfusing brain slices with medium devoid of glucose and oxygen elicits rapid decreases in phosphocreatine, ATP, intracellular pH, and in the evoked field potential recorded in the dentate gyrus. AMP and creatine rise during this period, while ADP and lactate levels remain unchanged. Cyclic AMP exhibits a transient increase in concentration. With the exception of ADP and lactate, these responses are very similar to those observed during in vivo ischemia. The return of glucose and oxygen to the incubation medium reverses these metabolic and electrophysiological effects and also leads to pronounced elevations in cyclic nucleotide concentrations. Metabolite concentrations approach, but do not reach, in vitro steady state levels during the first 30 min of recovery. Total adenylate and creatine steady state levels are approximately 50% of in vivo concentrations. The results suggest that, although hippocampal slices differ metabolically from in vivo tissue, they exhibit a similar pattern of metabolic responses to ischemic and reflow conditions.
 ...
PMID:An in vitro model of ischemia: metabolic and electrical alterations in the hippocampal slice. 632 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>