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)

Optical fluorescence and reflectance measurements have been used to map the distribution of metabolic states in three dimensions in the gerbil brain with a spatial resolution of 200 microns an a time resolution of 4-6 s. In Mongolian gerbils anesthetized with pentobarbital, the redox states of the nicotinamide adenine dinucleotide (NADH) and flavoprotein components of the electron transport chain exhibit two distinct phases during the wave of spreading depression: (1) a transient period of oxidation and (2) a prolonged period of reduction, during which the cytochromes are reduced, and the hemoglobin is predominantly in the deoxy form. These data are interpreted as indicating that the energy demand placed on the gerbil brain during such spreading depression wave is sufficient to drive the brain temporarily hypoxic.
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PMID:Time resolved 3-dimensional recording of redox ratio during spreading depression in gerbil brain. 230 48

The effects of methyl-group acceptors such as glycine, guanidinoacetic acid, and nicotinamide on cholesterol metabolism and phosphatidylcholine(PC) biosynthesis were investigated with rats fed a 25% casein diet containing cholesterol with or without methionine supplement. The effect of ethanolamine, an indirect methyl-group acceptor via phosphatidylethanolamine(PE) formation, was also compared with those of methyl-group acceptors. The methyl-group acceptors and ethanolamine decreased or tended to decrease plasma total cholesterol level when added to the 25% casein diet. These compounds also significantly depressed the methionine-induced enhancement of plasma cholesterol level. The activity of PE N-methyltransferase was decreased by the addition of glycine, guanidinoacetic acid, and nicotinamide, but not ethanolamine, to the reaction mixture when assayed using the postmitochondrial fraction of liver homogenate, suggesting that PE N-methyltransferase activity can be depressed by glycine N-methyltransferase, guanidinoacetic acid N-methyltransferase, and nicotinamide N-methyltransferase systems. The PE N-methyltransferase activity in liver microsomes, however, did not decrease in response to the dietary addition of methyl-group acceptors. The in vitro incorporation of [CH3-14C]methionine into PC of liver slices was also significantly inhibited by the addition of glycine and nicotinamide, but not guanidinoacetic acid and ethanolamine, to the incubation medium. It is suggested that methyl-group acceptors can decrease plasma cholesterol level at least in part through the depression of PC biosynthesis via PE N-methylation pathway, and that the mechanism for the plasma cholesterol-lowering effect of ethanolamine is different from that of methyl-group acceptors.
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PMID:Effects of methyl-group acceptors on the regulation of plasma cholesterol level in rats fed high cholesterol diets. 253 19

The effects of 5-azacytidine (5-AC) administration on the hepatic cytochrome P-450 systems of mice were studied. A single i.p. dose of 5-AC (25 mg/kg) to male Swiss-Webster mice caused about a 50% depression of microsomal cytochromes P-450 and b5 and of ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities. Depression was greatest 24 h after treatment; by 48 to 72 h, cytochromes and drug metabolism had returned to near control values. Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also depressed by 5-AC, whereas reduced nicotinamide adenine dinucleotide-cytochrome c reductase was not. Incubation of 5-AC with microsomes produced no effect on drug metabolism. The prolongation of hexobarbital sleeping time by 5-AC showed that drug metabolism is also impaired by 5-AC in vivo. These studies may have important clinical implications when certain drugs are coadministered with 5-AC.
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PMID:Depression of the hepatic cytochrome P-450 monooxygenase system by treatment of mice with the antineoplastic agent 5-azacytidine. 257 31

The use of fluorescent calcium indicator, Indo-1, was evaluated for measuring changes in intracellular free calcium during electrical stimulation and anoxia in hippocampal slices. Fluorescence was measured from slices illuminated with brief (3 ns) light pulses (337 nm wavelength) from a nitrogen laser. This method of illumination produced more intense fluorescence than illumination with light from filtered xenon or mercury arc lamps, and prevented loss of electrical excitability encountered following continuous UV illumination. Background fluorescence in control slices (without Indo-1) was considerable, often approaching 50% of that obtainable after dye loading. A more serious concern, however, was that a large fraction (approximately 10%) of the background fluorescence was labile to both electrical stimulation and anoxia. This fluorescence results from changes in the reduction/oxidation (redox) state of nicotinamide adenine dinucleotide (NAD), which fluoresces in its reduced (NADH) but not oxidized (NAD+) form. Qualitative changes in free calcium could be measured by first determining the ratio of change in NADH fluorescence at 405 and 485 nm (the wavelengths of light used to measure calcium with Indo-1) prior to dye loading. Any arbitrary baseline could be selected as long as the ratio for the baseline at 405 and 485 nm was identical to that determined for labile NADH. By application of this compensation procedure, it was determined that intracellular calcium rose abruptly during the onset of anoxia and again during the spreading depression-like loss of ion homeostasis which inevitably occurred during anoxia in these slices.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indo-1 measurements of intracellular free calcium in the hippocampal slice: complications of labile NADH fluorescence. 272 10

Transducin is the substrate for a pertussis toxin-catalyzed ADP-ribosylation in isolated retinal rod disk membranes [(1984) J. Biol. Chem. 259, 23-26]. The effects of the toxin on the light responses of intact dark-adapted rods were studied. Applied close to a rod outer segment in a retinal slice, pertussis toxin depolarized the rod by a few millivolts and produced a long-lasting depression of light responses, effects which depended on penetration of toxin into rods. Nicotinamide, an inhibitor of ADP-ribosylation, not only blocked the action of the toxin, but also reversed the effects once established. The action of nicotinamide itself on rods indicates the presence of endogenous ADP-ribosyltransferases which may constitute a control system modulating phototransduction. Inhibition of phospholipase C by neomycin had only transient effects indicating that the cGMP, rather than a phosphoinositide, pathway is primary in vertebrate phototransduction. Rapid reversal of pertussis toxin action suggests possible clinical applications of nicotinamide or congeners to the treatment of disease caused by ADP-ribosylating bacterial toxins.
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PMID:Block of light responses of salamander rods by pertussis toxin and reversal by nicotinamide. 283 Oct 82

Young rats were fed a niacin-deficient diet with and without 15 g/kg supplementary L-leucine. Both groups grew slowly for 5 wk and showed no difference in the severity of their condition. Nor did their 14CO2 production differ after intraperitoneal dosing with [methylene-14C]tryptophan. In a 2 X 3 X 3 multifactorial trial with a niacin-free basal diet, the effects of 15 g/kg supplementary leucine were compared with isonitrogenous glycine supplements. Half of the diets were also marginally deficient in pyridoxine and resulted in slower growth, but no interactive effect with leucine. The leucine supplement depressed excretion of N1-methylnicotinamide only in the groups receiving supplementary tryptophan. It was also associated with a depression in the level of nicotinamide nucleotides in the rats' livers that was not eliminated by addition of either 25 mg/kg nicotinic acid or 1 g/kg L-tryptophan. The existence of pellagra in Hyderabad, India, has been hypothesized to result from excessive leucine in the diet rather than from a deficiency of niacin/tryptophan. Neither our results with rats nor those of others appear to provide support for this hypothesis.
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PMID:Leucine excess and niacin status in rats. 295 74

Pretreatment with 20 mg/kg nicotinamide 3 days prior to a single intraperitoneal 6 mg/kg adriblastin injection, followed by repeated injections every second days for 1 week, prevented cardiac contractility disorders in adriblastin-treated rats, while their cardiac contractility was less prone to hypoxic depression and recovered better at subsequent reoxygenation.
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PMID:[Prevention of disorders of cardiac contractility with nicotinamide in adriblastin -related damage]. 297 17

Subcellular fractionation of bovine thyroid tissue by differential pelleting and isopycnic gradient centrifugation in a zonal rotor indicated that NAD(+) glycohydrolase is predominantly located and rather uniformly distributed in the plasma membrane. Comparison of NAD(+) glycohydrolase activities of intact thyroid tissue slices, functional rat thyroid cells in culture (FRT(l)) and their respective homogenates indicated that most if not all of the enzyme (catalytic site) is accessible to extracellular NAD(+). The reaction product nicotinamide was predominantly recovered from the extracellular medium. The diazonium salt of sulphanilic acid, not penetrating into intact cells, was able to decrease the activity of intact thyroid tissue slices to the same extent as in the homogenate. Under the same conditions this reagent almost completely abolished NAD(+) glycohydrolase activity associated with intact thyroid cells in culture. The triazine dye Cibacron Blue F3GA and its high-M(r) derivative Blue Dextran respectively completely eliminated or caused a severe depression in the NAD(+) glycohydrolase activity of FRT(l) cells. The enzyme could be readily solubilized from bovine thyroid membranes by detergent extraction, and was further purified by gel filtration and affinity chromatography on Blue Sepharose CL-6B. The overall procedure resulted in a 1940-fold purification (specific activity 77.6mumol of nicotinamide released/h per mg). The purified enzyme displays a K(m) of 0.40mm for beta-NAD(+), a broad pH optimum around pH7.2 (0.1 m-potassium phosphate buffer) and an apparent M(r) of 120000. Nicotinamide is an inhibitor (K(i) 1.9mm) of the non-competitive type. The second reaction product ADP-ribose acts as a competitive inhibitor (K(i) 2.7mm). The purified enzyme splits beta-NAD(+), beta-NADP(+), beta-NADH and alpha-NAD(+) at rates in the relative proportions 1:0.75:<0.02:<0.02 and exhibits transglycosidase (pyridine-base exchange) activity. Anionic phospholipids such as phosphatidylinositol and phosphatidylserine inhibit the partially purified enzyme. A stimulating effect was observed upon the addition of histones.
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PMID:Topography, purification and characterization of thyroidal NAD+ glycohydrolase. 298 95

Inhibition of ADP phosphorylation by both glycolysis and mitochondria in P388D1 cells exposed to H2O2 is described. Net glucose uptake and lactate production were inhibited by oxidant exposure (ED50 = 50-100 microM). Glycolysis was specifically inactivated at the glyceraldehyde-3-phosphate dehydrogenase step by three independent mechanisms: (a) direct inactivation of the intracellular enzyme (ED50 approximately equal to 100 microM); (b) reduction of the intracellular concentration and redox potential of its nicotinamide cofactors; and (c) a cytosolic pH shift further from the enzyme optima. Consistent with inhibition of glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step, a rise in the intracellular concentration of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-bisphosphate was observed. The calculated combined inhibition of glyceraldehyde-3-phosphate dehydrogenase activity could be reasonably correlated with the depression in glycolytic flux rate with the appropriate modeling. The steady-state contribution by mitochondria to the total intracellular ATP pool was indirectly determined by the use of various metabolic inhibitors and was found to rapidly decline following exposure to 300-800 microM H2O2. The inhibition of ADP phosphorylation appeared to be related more to the direct inhibition of the ATPase-synthase complex rather than to the diminished capacity of the respiratory chain for coupled electron transport. Both the estimated rates of ADP phosphorylation by glycolysis and mitochondria and the estimated rate of ATP hydrolysis by ongoing metabolism were utilized to model the approximate decline in intracellular ATP expected at 15-min exposure to various H2O2 concentrations. Theoretical calculations and the measured intracellular ATP status were in good agreement. Oxidant exposure for 15 min resulted in dose-dependent killing of the cells (ED50 = 500 microM), indicating a close correlation between H2O2-mediated loss of intracellular ATP and cell viability. The possible contribution of impaired energy homeostasis during oxidant-mediated injury to the process of cell dysfunction and death is discussed.
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PMID:Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide. 333 86

Emotional painful stress was shown to result in a significant depression of the portal vein contractile function accompanied by its decreased adrenoreactivity and its increased dependence on changes of external temperature, calcium and glucose. Experimental myocardial infarction caused similar disturbances of the contractile function and reactivity of the portal vein. The data obtained suggested that these shifts were induced by the infarction-concomitant stress. The disturbances revealed can be prevented or limited to a considerable extent by a pretreatment of animals with alpha-adrenoblocker phentolamine, inhibitor of the lipid peroxidation antioxidant ionol, and inhibitor of lipases nicotinamide. The high efficiency of such a protection indicates that the processes blocked by these inhibitors are important links in the pathogenetic chain of stress damage to the portal vein.
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PMID:Disturbance of contractile function of vena portae in stress and infarction and its prevention. 405 43


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