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)

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

The effect of the ganglioside GM1 was studied in a focal cerebral ischemia model in 30 cats consisting of 2 hours of middle cerebral artery occlusion followed by 4 hours of recirculation. The cerebrocortical electrical activity, extracellular potassium activity, and microcirculation indicated by NAD/NADH fluorescence were measured during occlusion as well as during recirculation in the core of the middle cerebral artery territory, while the cerebral metabolic rate for glucose (ICMRgl) was measured at the end of recirculation. The cats were classified into either mildly or moderately severe stroke groups based on the depression of the cerebrocortical electrical activity on the occluded side. Of 12 cats with only a mild stroke, six were administered GM1 intravenously 30 minutes after occlusion, while six cats were not treated. Of 12 cats with a moderate stroke, six were treated and six were left untreated. In six additional cats, only a sham insult was undertaken. In the cats with mild stroke, GM1 treatment significantly increased lCMRgl in the peripheral middle cerebral artery territory compared with the untreated cats; for the six treated cats, lCMRgl was normalized toward the control level, whereas it was depressed in the six untreated cats. There were no other significant effects of GM1 treatment on the other measured parameters. A potential protective effect of anesthesia is discussed.
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PMID:Effect of GM1 ganglioside after focal cerebral ischemia in halothane-anesthetized cats. 272 48

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

In reviewing our own and other work, it is clear that pertussis toxin treatment of neutrophils causes a time- and concentration-dependent inhibition of granule enzyme secretion induced by formylmethionylleucylphenylalanine (fMet-Leu-Phe), C5a, leukotriene (LT) B4 and platelet-activating factor (PAF). Chemotaxis, O2- generation, aggregation, and arachidonic acid production induced by fMet-Leu-Phe are also inhibited by pertussis toxin. Granule enzyme release caused by A23187 or phorbol 12-myristate 13-acetate is not inhibited. The inhibition of neutrophil function correlates closely with the NAD-ribosylation of a 41,000-dalton protein in the neutrophil plasma membrane, presumably the GTP-binding regulatory protein Ni. Pertussis toxin treatment prevents or obtunds the increased influx of Ca2+ induced by fMet-Leu-phe and LTB4, but not that caused by stimulation of neutrophils with PAF. Pertussis toxin prevents the receptor-induced breakdown of polyphosphoinositides in intact neutrophils and isolated membrane and prevents or decreases the production of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol. The hypothesis advanced by us and others is that pertussis toxin interacts with a GTP-binding regulatory protein identical or similar to Ni, which couples receptor-chemotactic factor interaction to phospholipase C activation. Inhibition of the activation prevents the production of IP3 and the resulting release of Ca2+ from intracellular stores and of 1,2-diacylglycerol and thus, the activation of protein kinase C. The lack of these two mediators is the immediate cause of the depression of neutrophil activation resulting from pertussis toxin. Some of the limitations and uncertainties of our present knowledge with respect to this hypothesis are discussed.
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PMID:Pertussis toxin as a probe of neutrophil activation. 301 23

The effect of asphyxia and subsequent resumption of respiration on the content of adenine nucleotides and some amino acids in heart tissue and mitochondria, as well as respiration of heart mitochondria was studied in rats. The depression of cardiac contractile function during asphyxia showed a better correlation with losses in mitochondrial adenine nucleotides (ATP + ADP + AMP) than those in cardiac tissue. The decrease in the heart work index was accompanied by a decrease in state 3 respiration with glutamate and malate as well as uncoupled respiration with these substrates. This did not occur with succinate. Nonphosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by asphyxia, when respiratory substrates of both types were used. The decreased level of glutamic acid in the tissue and mitochondria of asphyxic hearts was simultaneously observed with a significant increase of alanine in cardiac tissue and of aspartic acid in the mitochondria. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during asphyxia were associated with a reduction of glutamic acid level in mitochondria. The recovery of cardiac function during resumption of respiration was related to the restoration of mitochondrial respiration supported by glutamate and malate, as well as to the restoration of mitochondrial adenine nucleotides and glutamic acid. The results suggest that the depression of cardiac function caused by acute respiratory hypoxia may be attributed to impairment of electron transport, particularly in complex I of the respiratory chain and changes in metabolism of glutamic acid.
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PMID:The relationship between the cardiac contractile function, adenine nucleotides and amino acids of cardiac tissue and mitochondria at acute respiratory hypoxia. 361 64

Changes in microcirculation, the NAD/NADH redox state, and electrical activity during 2 hours of ischemia and 4 hours of reperfusion produced by middle cerebral artery occlusion and release were studied in cats. Twelve animals were classified into three groups of ischemia (mild, moderate, and severe) based on the severity of electrocorticographic (ECoG) depression at the end of the recovery period. Four animals were studied as controls. Occlusion of the middle cerebral artery (MCAO) resulted in a marked but similar degree of reduction in cerebral blood flow (CBF) in all three groups. After this initial change, CBF increased continuously during occlusion in the mild group. CBF in the moderate and severe groups remained at the same low level during the entire period of MCAO. Immediately after MCAO, NAD reduction was increased by approximately 50% in all groups. At the end of MCAO, while the NAD/NADH redox state returned to its pre-ischemic reference level in the severe group, it remained markedly reduced in the mild and moderate groups. Removal of the clip led to slight reactive hyperemia in the mild and severe groups but not in the moderate group. Immediately after recirculation, NAD/NADH redox was shifted toward oxidation in all groups. However, this reoxidation of NADH was only partial in the mild and moderate groups, and a pronounced hyperoxidation occurred in the severe group. In spite of the similar behavior of CBF in the recovery period, a marked secondary NAD reduction occurred in the moderate group during the recirculation period. It is suggested that this represents cessation of mitochondrial electron transport in the dying cells, accompanied by stimulated anaerobic glycolysis in other cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of microcirculatory, NAD/NADH, and electrocorticographic changes in cat brain cortex during ischemia and recirculation. 372 9

The effect of acute hypoxia on adenine nucleotides, glutamate, aspartate, alanine and respiration of heart mitochondria was studied in rats. The losses of intramitochondrial adenine nucleotides (ATP+ADP+AMP) during hypoxia were related to depression of state 3 respiration supported by glutamate and malate, as well as decrease in uncoupled respiration. Hypoxia had less prominent effect on succinate-dependent state 3 respiration. Non-phosphorylating (state 4) respiratory rates and ADP/O ratios were slightly affected by oxygen deprivation. Glutamate fall in tissue and mitochondria of hypoxic hearts was concomitant with significant increase in tissue alanine and mitochondrial aspartate. The losses of intramitochondrial ATP and respiratory activity with NAD-dependent substrates during hypoxia were related to a decrease in mitochondrial glutamate. The results suggest that hypoxia-induced impairment of complex I of respiratory chain and a loss of glutamate from the matrix may limit energy-producing capacity of heart mitochondria.
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PMID:Adenine nucleotides, glutamate and respiratory function of heart mitochondria during acute hypoxia. 375 8

Local cerebral glucose utilization (lCMRgl), NADH fluorescence, cerebral blood flow (CBF), electrocortical activity (ECoG) and histology were studied during a 4 hr recovery period following 2 hrs of left middle cerebral artery (MCA) occlusion in cats. Changes in relative reduced pyridine nucleotides and CBF were measured by fluororeflectometry, ECoG was obtained from the left middle ectosylvian gyrus (MEG), and lCMRgl was measured at the end of the recovery period autoradiographically with 14-C-2-deoxyglucose. A sham group was comprised of 4 cats. The ten animals subjected to the stroke were classified into 3 groups based on the mean amplitude of the ECoG at the end of the ischemic period. At the end of the recovery period, the relative reduced pyridine nucleotides showed a 22.5% oxidation (oxidation of NADH), a 66.2% reduction (reduction of NAD) and a 3.0% reduction compared to the sham group in the severe, moderate and mild groups, respectively. LCMRgl of the left MEG in the severe group was 64.2% of the corresponding sham value, whereas lCMRgl in the moderate and mild groups were 124.8% and 132.0% of the sham, respectively. CBF at the end of the recovery period ranged from 28.1% to 83.0% of the sham value, although there was no significant difference among these groups. Histologically, a large portion of the neurons in the left MEG in the severe group showed ischemic neuronal changes, while the damage was less severe in the moderate and mild groups. On the basis of these data, it is suggested that a relative substrate deficiency and/or a loss of mitochondrial enzymatic pool size may occur in the animals comprizing the severe group. Conversely, anaerobic glycolysis may be activated in the moderate group, while the mild group exhibits an increase in glucose metabolism that is most likely aerobic. A gradient in the magnitude of changes in lCMRgl was noted from the central MCA territory to the surrounding brain regions in the ischemic hemisphere. In addition, there was a mild, but statistically significant (p less than 0.05), depression in lCMRgl with no histological damage in the non-ischemic hemisphere of the severe group.
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PMID:Cerebral glucose metabolism during the recovery period after ischemia--its relationship to NADH-fluorescence, blood flow, EcoG and histology. 376 74

In anaesthetized rats kept on normal diet an i.v. infusion of NAD (200 nmole X kg-1 X X min-1) induced a decrease in renal plasma flow (CPAH), glomerular filtration rate (GFR) and electrolyte excretion accompanied by an increase in plasma adenosine concentration. Separate infusions of a small dose of NAD (50 nmole X kg-1 X min-1) or dipyridamole (25 micrograms X kg-1 X min-1) did not affect renal function or plasma adenosine concentration. However, when the above small doses of both agents were given simultaneously, GFR, CPAH and electrolyte excretion fell significantly, indicating potentiation of NAD action by dipyridamole, associated with increased plasma adenosine level. An i.v. infusion of furosemide failed to abolish the depression of renal function in response to NAD. The data suggest that the causal factor of this depression was adenosine and not NAD itself.
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PMID:Effects of dipyridamole and furosemide on renal function during adenine dinucleotide infusion in rats. 378 6

Anti-My-26, a mouse monoclonal IgG1 antibody, was raised against human granulocytes and has been shown to inhibit luminol-enhanced, glucose-independent chemiluminescence (CL) of human granulocytes (or monocytes) responding to the soluble secretagogues A23187 or ionomycin (calcium ionophores) and phorbol myristate acetate (PMA). Anti-My-26 inhibition of CL was reversible and was dependent on both secretatogue and monoclonal antibody concentration. This inhibition appeared to be directed at the component of granulocyte CL that is independent of NAD(P)H-oxidase-catalyzed formation of superoxide anion, because neither opsonized zymosan-stimulated CL nor the PMA-induced decrease in NAD (P)H-associated autofluorescence was affected by anti-My-26. In addition, ionomycin, over a wide concentration range, failed to generate any decrease in granulocyte autofluorescence. The A23187-induced CL inhibited by anti-My-26 was correlated with its depression of oxygen consumption. Furthermore, anti-My-26 was not cytotoxic and did not itself induce oxidative metabolism when used as a stimulant. Binding of anti-My-26 to phagocytic cells was not decreased by pre-exposure of cells to either A23187 or PMA. Evidence is presented to suggest that the binding of anti-My-26 to the granulocyte surface inhibits the oxidative response to calcium ionophore and PMA by blocking a common pathway(s) stimulated by these different secretagogues.
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PMID:Anti-My-26: a monoclonal antibody inhibiting human phagocyte chemiluminescence. 391 9


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