Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well known that excessive calcium entry into the myocardial cells may contribute considerably to damage of the heart caused by postischemic reperfusion. The effect of increased calcium entry on hemodynamics, energy metabolism and histochemically estimated enzyme activities in isolated, perfused (Langendorff) rat heart preparation was investigated using calcium paradox (CaPX) as a model. After a 15 min period of stabilized perfusion of the heart, CaPX was induced at 37 degrees C by 2.5 min lasting calcium depletion (calcium-free perfusion) and subsequent calcium repletion (10 min). Changes induced by CaPX concerned loss of electrical and mechanical activities of the heart, significant decreases in coronary flow and ATP, ADP and the total content of adenine nucleotides in tissue as well as considerable depression in ATPases, SDH, beta-HBDH, LDH and glycogen phosphorylase activities in the myocardium. Diltiazem in concentration of 4.0 mumol.l-1 applied prior to calcium depletion and during calcium repletion prevented partially the deterioration of cardiac function by improving contractility and electrical activity of the heart as well as the coronary flow. The effect of diltiazem in concentration of 0.4 mumol.l-1 was less expressed. After both concentrations of diltiazem used, a better preserved ultrastructure, higher activities of the enzymes investigated, significantly higher ATP and total adenine nucleotide levels were seen in the myocardium as compared to the untreated controls.
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PMID:Partial prevention of calcium paradox in isolated perfused rat hearts by diltiazem. 252 34

Several hepatotoxic agents with varied chemical mechanisms of toxicity (acetaminophen, diquat, and CCl4) depress membrane calcium pumps and/or enhance the permeability of membranes to calcium. To probe the relevance of these findings to maintenance of calcium homeostasis after toxins in vivo, we measured the activity of glycogen phosphorylase a, as an index of cytosolic free [Ca2+], in freeze-clamped liver samples obtained at several times after the toxin dose. Both acetaminophen and diquat caused significant increases of phosphorylase a activity, and activity remained elevated for several hours after the dose. Significantly, the administration prior to diquat of desferrioxamine, which offers protection against the liver necrosis and depression of microsomal Ca2+ accumulation observed after diquat alone (Tsokos-Kuhn et al., Mol Pharmacol 34: 209-214, 1988), decreased phosphorylase activation. Activation of phosphorylase was observed also after CCl4 administration, as previously reported by Long and Moore (Biochem Pharmacol 35: 4131-4137, 1986). We conclude that perturbations in liver membrane Ca2+ regulation observed after administration of these hepatotoxins in vivo correlate directly with phosphorylase a activity, thereby providing additional in vivo evidence for an alteration of Ca2+ homeostasis early in the development of the liver damage produced by these chemicals.
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PMID:Evidence in vivo for elevation of intracellular free Ca2+ in the liver after diquat, acetaminophen, and CCl4. 278 60

Kinetic properties of regulatory enzymes of glycolysis in liver of the mouse, Zapus hudsonius, were modified during hibernation, the probable mechanism being covalent modification. Liver glycogen phosphorylase activity was strongly depressed during both short (less than 24 h) and long (5-8 days) term hibernation, the mechanism involving a decrease in both the percentage of enzyme in the active a form and the total amount (a + b) of enzyme expressed. Phosphofructokinase showed kinetic changes (a 2.5-fold increase in Ka for fructose-2,6-P2, 4- and 3.7-fold decreases in I50 values for ATP and citrate, compared to euthermic controls) in liver of hibernators indicative of phosphorylation inactivation of the enzyme. Measured levels of fructose-2,6-P2 in liver did not change during hibernation. Changes in pyruvate kinase kinetics in liver from long term hibernators similarly indicated enzyme phosphorylation in the depressed state (Ka for fructose-1,6-P2 increased 4.4-fold, I50 for L-alanine decreased 6.3-fold). Apparent covalent modification of glycolytic enzymes during hibernation may serve two functions: depression of glycolytic activity as part of the general metabolic rate depression of hibernation, or reorganization of fuel use in the hibernating state to limit carbohydrate catabolism and promote gluconeogenesis.
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PMID:Regulation of liver metabolism by enzyme phosphorylation during mammalian hibernation. 294 58

An examination of the kinetic parameters of phosphofructokinase, pyruvate kinase and glycogen phosphorylase, and the cellular concentration of fructose 2,6-bisphosphate during anoxia in the turtle Pseudemys scripta showed that the total activity of glycogen phosphorylase, and the phosphofructokinase inhibition constants for citrate and ATP were decreased in anoxic turtle brain. These results suggest that the ability of turtle brain to survive extended periods of anoxia is the result of metabolic rate depression regulated, at the molecular level, by enzyme inactivation through anoxia-induced covalent modification.
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PMID:Anoxic brain function: molecular mechanisms of metabolic depression. 296 46

In response to added catecholamines, isolated trout (Salmo gairdneri) hepatocytes substantially increase the output of glucose into the surrounding medium. This effect is due to activation of glycogen breakdown concomitant with increases in gluconeogenesis and cell respiration. Each metabolic parameter is activated to a similar extent. In hormone-treated and untreated cells, glycogenolysis accounts for more than 97% of glucose production. Activation of glycogen phosphorylase is implicated in the degradation of cell glycogen, while increased flux through the gluconeogenic pathway from lactate is associated with inactivation of pyruvate kinase, possibly through enzyme phosphorylation as indicated by the activity ratio measured at low and saturating concentrations of phosphoenolpyruvate. From studies with specific adrenergic agonists and antagonists, we conclude that stimulation of glycogenolysis and gluconeogenesis in trout hepatocytes is consistent with a beta-adrenergic effect. Results are inconclusive with respect to catecholamine-mediated activation of cell respiration. None of the monitored cell acid-base variables (pH, PCO2, [HCO3-]) are implicated in the catecholamine-dependent changes in metabolic output of hepatocytes. Imposed hypercapnic conditions (increased medium PCO2 and decreased medium pH), which cause changes in cell acid-base parameters, result in a depression of lactate oxidation and gluconeogenesis, while the rate of glycogenolysis is not affected. In addition, the total amounts of glycogen phosphorylase and pyruvate kinase assayable are negatively affected by hypercapnic treatment of hepatocytes. Under hypercapnic conditions, cells are highly responsive to adrenergic agonists. It appears that--especially in the long term--the catecholamine-dependent activation of gluconeogenesis may compensate for the acid-base-dependent shortfall in glucose output by the liver.
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PMID:Interactive effects of catecholamines and hypercapnia on glucose production in isolated trout hepatocytes. 313 Nov 87

Rats were treated with Escherichia coli endotoxin (ET) either acutely or chronically or rendered septic by cecal ligation and puncture. At 6 h after ET injection, at various intervals of continuous ET infusion, and at 17-18 h after the onset of peritonitis, animals were killed and hepatocytes were isolated. Cytosolic [Ca2+] ([Ca2+]c) was measured by quin 2 during the resting state and after stimulation with epinephrine and vasopressin. Basal and epinephrine-, vasopressin- and glucagon-stimulated glycogen phosphorylase activity were also determined. In hepatocytes from acutely ET-treated rats, resting levels of [Ca2+]c were decreased 46% from 245.8 +/- 11.0 to 131.0 +/- 8.5 nM (n = 4-6, P less than 0.05). In septic rats a 39.5% decrease was noted [i.e., from 154.0 +/- 17.7 (n = 4, sham) to 93.3 +/- 91 nM (n = 5, septic, P less than 0.05)]. These decreased [Ca2+]c levels were associated with changes of glycogen phosphorylase activity in a manner suggesting a cause and effect relationship; e.g., acute ET treatment resulted in greater than 80% depression of phosphorylase a activity, whereas sepsis induced a 58% decrease in the activity of this enzyme. In ET-infused rats the resting level of [Ca2+]c and its response to hormonal stimulation were not different from hepatocytes of saline-infused rats, although glycogen phosphorylase activity was less responsive to these hormones. The effect on the enzyme's response to Ca2+-mobilizing hormones was more marked than to glucagon. This is consistent with the concept that information flow in the Ca2+-messenger system is a site of metabolic lesions produced by endotoxicosis and sepsis.
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PMID:Rat liver free cytosolic Ca2+ and glycogen phosphorylase in endotoxicosis and sepsis. 353 41

The study of patterns of serum AST, ALT, CPK, LDH, and glycogen phosphorylase (GP) activity following bicycle ergometry in 26 male patients 1 to 1.5 months after myocardial infarction demonstrated no increase in AST, ALT and CPK activity, whereas total LDH activity was increased, with a tendency to elevated LDH-1 and LDH-2 fractions, as compared to the baseline, in those cases where exercise was discontinued because of ST depression. Patients with favorable response to bicycle ergometry that continued until the submaximum heart rate for a given age was achieved showed a tendency to elevated LDH-5 that may be a physiological response to exercise. The demonstrated increase in total GP activity, both in patients with exercise-induced ST depression and in those with elevated ST from the leads corresponding to the site of myocardial infarction, may reflect stress-induced reversible ischemia.
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PMID:[Effect of physical loading on serum enzyme activity in post-myocardial infarct patients]. 370 99

Freshwater turtles Trachemys scripta elegans endure prolonged severe hypoxia, and even complete anoxia, while diving or hibernating underwater. Metabolic adaptations supporting survival include the activation of glycogenolysis and glucose output from liver, as well as strong metabolic rate depression. The present study analyzes the enzymes of both the phosphorolytic (glycogen phosphorylase, phosphorylase b kinase, cAMP-dependent protein kinase) and glucosidic (alpha-glucosidase) pathways of glycogenolysis in turtle organs. Turtles were subjected to 5 hr of submergence in N2-bubbled water at 7 degrees C and then activities of phosphorolytic and glucosidic enzymes were assayed in liver, heart, brain, and red and white skeletal muscle, and compared with aerobic controls. In vitro incubations also assessed protein kinase A control of phosphorolytic enzymes. A functional enzyme cascade system for the activation of glycogen phosphorylase was found in all organs, and both phosphorylase and phosphorylase kinase were stimulated by in vitro incubation with the catalytic subunit of cAMP-dependent protein kinase. Anoxic submergence led to significant increases in phosphorylase activities in liver and heart (phosphorylase a rose 2- and 2.5-fold, respectively) but phosphorylase kinase and protein kinase A activities in liver were reduced after 5 hr exposure. Both acidic (pH 4) and neutral (pH 7) forms of alpha-glucosidase were detected in all five organs with highest activities in liver. Activity of acid alpha-glucosidase, which degrades lysosomal glycogen, increased by 2-fold in liver during anoxic submergence. The data show that glycogen breakdown in turtle liver during anoxic submergence may result from coordinated activations of both the cytoplasmic phosphorolytic and the lysosomal glucosidic pathways of glycogenolysis.
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PMID:Enzymatic control of glycogenolysis during anoxic submergence in the freshwater turtle Trachemys scripta. 758 17

The alkali soluble fraction of the sepia shell possesses both anticonvulsant and hypoglycemic effect. The investigation regarding the fate of the blood sugar during the hypoglycemia revealed that the sepia shell extract acts as a glycogenic agent by mobilising the blood sugar towards liver glycogen reserve through the modulation of the enzymes glycogen phosphorylase a and ab in normal and streptozotocin diabetic mice. The glucose tolerance test (GTT) showed a depression in the GTT curve in experimental mice. The available literature on the biochemistry of the shell reveals that it contains glucosamines and some amino acid residues. The presence of amine group may resemble the sulfonylureas like tolbutamide which also possesses both anticonvulsant and hypoglycemic effect.
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PMID:Glycogenic effect of an alkali soluble fraction from sepia shell. 781 87

Anoxia-tolerant animal models are crucial to understand protective mechanisms during low oxygen excursions. As glycogen is the main fermentable fuel supporting energy production during oxygen tension reduction, understanding glycogen metabolism can provide important insights about processes involved in anoxia survival. In this report we studied carbohydrate metabolism regulation in the central nervous system (CNS) of an anoxia-tolerant land snail during experimental anoxia exposure and subsequent reoxygenation. Glucose uptake, glycogen synthesis from glucose, and the key enzymes of glycogen metabolism, glycogen synthase (GS) and glycogen phosphorylase (GP), were analyzed. When exposed to anoxia, the nervous ganglia of the snail achieved a sustained glucose uptake and glycogen synthesis levels, which seems important to maintain neural homeostasis. However, the activities of GS and GP were reduced, indicating a possible metabolic depression in the CNS. During the aerobic recovery period, the enzyme activities returned to basal values. The possible strategies used by Megalobulimus abbreviatus CNS to survive anoxia are discussed.
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PMID:Control of carbohydrate metabolism in an anoxia-tolerant nervous system. 2096 May 58


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