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)

Prion diseases are characterized by the conversion of the normal cellular prion protein (PrP(C)) into a pathogenic isoform (PrP(Sc)). PrP(C) binds copper, has superoxide dismutase (SOD)-like activity in vitro, and its expression aids in the cellular response to oxidative stress. However, the interplay between PrPs (PrP(C), PrP(Sc) and possibly other abnormal species), copper, anti-oxidation activity and pathogenesis of prion diseases remain unclear. In this study, we reported dramatic depression of SOD-like activity by the affinity-purified PrPs from scrapie-infected brains, and together with significant reduction of Cu/Zn-SOD activity, correlates with significant perturbations in the divalent metals contents. We also detected elevated levels of nitric oxide and superoxide in the infected brains, which could be escalating the oxidative modification of cellular proteins, reducing gluathione peroxidase activity and increasing the levels of lipid peroxidation markers. Taken together, our results suggest that brain metal imbalances, especially copper, in scrapie infection is likely to affect the anti-oxidation functions of PrP and SODs, which, together with other cellular dysfunctions, predispose the brains to oxidative impairment and eventual degeneration. To our knowledge, this is the first study documenting a physiological connection between brain metals imbalances, the anti-oxidation function of PrP, and aberrations in the cellular responses to oxidative stress, in scrapie infection.
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PMID:Oxidative impairment in scrapie-infected mice is associated with brain metals perturbations and altered antioxidant activities. 1170 72

Myocardial depression can be demonstrated following administration of endotoxin. Proposed mechanisms of endotoxin-induced myocardial dysfunction include the release of proinflammatory mediators, focal myocardial ischemia, and the presence of activated leukocytes within the myocardium. Recently, myocardial caspase activation and mitochondria-related apoptotic events (i.e., release of cytochrome c) were demonstrated in the failing septic heart. Here, we tested the hypothesis that immunosuppressors, cyclosporin A and tacrolimus (FK 506), would improve inflammation, heart nuclear apoptosis, and myocardial dysfunction in endotoxin-treated rats. Myocardial contractility was assessed using an isolated heart preparation. Heart leukocyte infiltration was assessed by measurement of heart myeloperoxidase activity. Leukocyte activation was studied using the intravital microscopy of the mesenteric venule. Apoptosis was detected as myocardial DNA fragmentation, downstream caspase activation, and mitochondrial cytochrome c release. Both cyclosporin A and FK 506 reduced heart leukocyte sequestration and venular adhesion in endotoxin-treated rats. Cyclosporin A, which blocks mitochondrial cytochrome c release, was able to reduce endotoxin-induced myocardial end-stage nuclear apoptosis and heart dysfunction, whereas tacrolimus had no such effects. These effects could be related to the unique properties of cyclosporin A to act on mitochondria.
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PMID:Protective effects of cyclosporin A from endotoxin-induced myocardial dysfunction and apoptosis in rats. 1185 Mar 35

The stress metabolic activities of Panax ginseng (P. ginseng) cells induced by low-energy ultrasound (US) were examined. P. ginseng cells in suspension cultures were exposed to 38.5 kHz US at two power levels (power density 13.7 and 61 mW/cm(3)) for 2 min. The US treatment caused rapid increase in the intracellular levels of polyphenol oxidase (PPO), peroxidase (PO), and phenylalanine ammonia lyase (PAL) and the production of polyphenols (PP) and phenolic compounds. The US-induced enzyme activities and phenolics production are part of plant stress responses to a mechanical stimulus. The much higher PPO activity and rate of PP production in the sonicated cultures are correlated to enzymatic browning, suggestive of physical damage and membrane permeabilization of the cells by US. The cells after sonication also showed decreased water content and cell volume, which may also be attributed to US-induced cell membrane permeabilization and water release. High-pressure shock and fluid shear stress arising from acoustic cavitation were regarded as the major causes of the responses. Nevertheless, the US exposure caused only temporary cell growth depression but no net loss of biomass yield of the culture.
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PMID:Ultrasound-induced stress responses of Panax ginseng cells: enzymatic browning and phenolics production. 1215 22

Free radical processes and antioxidant systems activities were studied before and after treatment in blood and saliva of 23 depressive patients with ICD-10 diagnosis--6 with depressive episode and 17 with recurrent depression. Compared to control, blood plasma Fe(2+)-rodamine induced chemiluminescence, total peroxidase and catalase activities increased and blood plasma superoxide eliminational activity as well as superoxide dismutase activity in erythrocytes decreased in patients before treatment. At the same time, total peroxidase activity, superoxide eliminational activity and catalase activity were elevated in the patient's saliva. After antidepressant treatment, positive dynamics for many parameters studied was more pronounced in responders. Saliva was shown to be potential biological material for "oxidative stress" assessment and for treatment efficacy evaluation in depression.
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PMID:[Free radical processes and antioxidant system in depression and treatment efficiency]. 1237 82

Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy. DTB-induced muscle weakness results from a reduction of acetylcholine (ACh) release by mechanisms that are not yet clear. The objective of this study was to determine if altered release of ACh during DTB-induced muscle weakness was due to impairments of synaptic vesicle exocytosis, endocytosis, or internal vesicular processing. We examined motor nerve terminals in the triangularis sterni muscles of DTB-treated mice at the onset of muscle weakness. Uptake of FM1-43, a fluorescent marker for endocytosis, was reduced to approximately 60% of normal after either high-frequency nerve stimulation or K(+) depolarization. Terminals ranged from those with nearly normal fluorescence ("bright terminals") to terminals that were poorly labeled ("dim terminals"). Ultrastructurally, the number of synaptic vesicles that were labeled with horseradish peroxidase (HRP) was also reduced by DTB to approximately 60%; labeling among terminals was similarly variable. A subset of DTB-treated terminals having abnormal tubulovesicular profiles in their centers did not respond to stimulation with increased uptake of HRP and may correspond to dim terminals. Two findings suggest that posttetanic "slow endocytosis" remained qualitatively normal: the rate of this type of endocytosis as measured with FM1-43 did not differ from normal, and HRP was observed in organelles associated with this pathway- coated vesicles, cisternae, as well as synaptic vesicles but not in the tubulovesicular profiles. In DTB-treated bright terminals, end-plate potential (EPP) amplitudes were decreased, and synaptic depression in response to 15-Hz stimulation was increased compared with those of untreated mice; in dim terminals, EPPs were not observed during block with D-tubocurarine. Nerve-stimulation-induced unloading of FM1-43 was slower and less complete than normal in bright terminals, did not occur in dim terminals, and was not enhanced by alpha-latrotoxin. Collectively, these results indicate that the size of the recycling vesicle pool is reduced in nerve terminals during DTB-induced muscle weakness. The mechanisms by which this reduction occurs are not certain, but accumulated evidence suggests that they may include defects in either or both exocytosis and internal vesicular processing.
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PMID:Impairment of synaptic vesicle exocytosis and recycling during neuromuscular weakness produced in mice by 2,4-dithiobiuret. 1246 44

Ischemia/reperfusion (I/R) injury remains an important problem in clinical organ transplantation. There is growing evidence that T lymphocytes, and activated CD4+ T cells in particular, play a key role in hepatic I/R injury. This study analyzes the role of signal transducer and activator of transcription 4 (Stat4) and Stat6 signaling in liver I/R injury. Using a partial lobar warm ischemia model, groups of wild-type (WT), T cell-deficient, Stat4-/Stat6-deficient knockout (KO) mice were assessed for the extent/severity of I/R injury. Ninety minutes of warm ischemia followed by 6 hours of reperfusion induced a fulminant liver failure in WT and Stat6 KO mice, as assessed by hepatocellular damage (serum alanine aminotransferase [sALT] levels), neutrophil accumulation (myeloperoxidase [MPO] activity) and histology (Suzuki scores). In contrast, T cell deficiency (nu/nu mice) or disruption of Stat4 signaling (Stat4 KO mice) reduced I/R insult. Unlike adoptive transfer of WT or Stat6-deficient T cells, infusion of Stat4-deficient T cells failed to restore hepatic I/R injury and prevented tumor necrosis factor alpha (TNF-alpha) production in nu/nu mice. Diminished TNF-alpha/Th1-type cytokine messenger RNA (mRNA)/protein elaborations patterns, along with overexpression of heme oxygenase-1 (HO-1)-accompanied hepatic cytoprotection in Stat4 KO recipients. In contrast, HO-1 depression restored hepatic injury in otherwise I/R resistant Stat4 KOs. In conclusion, Stat4 signaling is required for, whereas Stat4 disruption protects against, warm hepatic I/R injury in mice. The cytoprotection rendered by Stat4 disruption remains HO-1-dependent.
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PMID:Stat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotection. 1254 Jul 79

Methyl-jasmonate (MeJA) has been proposed to be involved in the evocation of defense reactions, as the oxidative burst in plants, substituting the elicitors or enhancing their effect. 48 h dark- and sterilely cultured (axenic) aeroponic sunflower seedling roots excised and treated with different concentrations of MeJA showed a strong and quick depression of the H(+) efflux rate, 1.80 microM MeJA totally stopping it for approximately 90 min and then reinitiating it again at a lower rate than controls. These results were wholly similar to those obtained with nonsterilely cultured roots and have been interpreted as mainly based on H(+) consumption for O(2)(*-) dismutation to H(2)O(2). Also K(+) influx was strongly depressed by MeJA, even transitorily reverting to K(+) efflux. These results were consistent with those associated to the oxidative burst in plants. MeJA induced massive H(2)O(2) accumulation in the middle lamella and intercellular spaces of both the root cap cells and the inside tissues of the roots. The native acidic extracellular peroxidase activity of the intact (nonexcised) seedling roots showed a sudden enhancement (by about 52%) after 5 min of MeJA addition, maintained for approximately 15 min and then decaying again to control rates. O(2) uptake by roots gave similar results. These and other results for additions of H(2)O(2) or horseradish peroxidase, diphenylene iodonium, and sodium diethyldithiocarbamate trihydrate to the reaction mixture with roots were all consistent with the hypothesis that MeJA induced an oxidative burst, with the generation of H(2)O(2) being necessary for peroxidase activity. Results with peroxidase activity of the apoplastic fluid were in accordance with those of the whole root. Finally, MeJA enhanced NADH oxidation and inhibited hexacyanoferrate(III) reduction by axenic roots, and diphenylene iodonium cancelled out these effects. Redox activities by CN(-)- preincubated roots were also studied. All these results are consistent with the hypothesis that MeJA enhanced the NAD(P)H oxidase of a redox chain linked to the oxidative burst, so enhancing the generation of O(2)(*-) and H(2)O(2), O(2) uptake, and peroxidase activity by roots.
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PMID:Redox-related peroxidative responses evoked by methyl-jasmonate in axenically cultured aeroponic sunflower (Helianthus annuus L.) seedling roots. 1276 45

Fe deficiency was imposed by omission of Fe (-Fe), or by inclusion of bicarbonate (supplied as 20 mM NaHCO3) in the nutrient solution in two contrasting peach rootstocks (GF-677; tolerant to Fe deficiency and Cadaman; sensitive to Fe deficiency) for 4 months. In the Fe-deprived leaves and roots, and especially in those treated with bicarbonate, a decrease in Fe concentrations was recorded. Omission of Fe resulted in an increase of the activity of root Fe(III)-chelate reductase (FCR) in both rootstocks, whereas FCR activity decreased in the bicarbonate-treated roots of Cadaman. The results obtained from the FCR assay were confirmed by an agarose-based staining technique used to localize FCR activity. Also, an agar-pH-test revealed that the roots of GF-677 exposed to (-Fe) treatment induced a strong H+ extrusion. In addition, Fe deficiency resulted in reduction of the total chlorophyll (CHL) content. Apart from the (-Fe)-treated leaves of GF-677, Fe deficiency caused a decline in the photosynthetic rate (P(n)) and stomatal conductance (g(s)), without changes of the intercellular CO2 concentration (C(i)), as well as a reduction in the maximum quantum yield of PSII (F(v)/F(m)) and the ratio between variable to initial fluorescence F(v)/F0. The above changes were particularly evident for the bicarbonate-treated leaves of Cadaman. On the other hand, Fe deficiency resulted in an increase of leaf superoxide dismutase (SOD) activity and a depression of catalase (CAT) activity in the leaves and roots, irrespective of the rootstock. Although the non-enzymatic antioxidant activity (FRAP values) was increased in the roots of both rootstocks exposed to -Fe treatment, however, FRAP values were stimulated in the (-Fe)-treated leaves of GF-677 and decreased in the bicarbonate-treated leaves of Cadaman. The H2O2 content was increased in Fe-deprived tissues except for the (-Fe)-treated leaves and roots of GF-677. As a result of Fe deficiency, peroxidase (POD) activity and isoform expression were diminished in the tissues of Cadaman. However, in the tissues of GF-677 subjected to -Fe treatment POD activity was increased whereas an additional POD isoform was detected in the roots suggesting that expression of POD isoforms might be an important attribute linked to the tolerance to Fe deficiency.
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PMID:Effects of 4-month Fe deficiency exposure on Fe reduction mechanism, photosynthetic gas exchange, chlorophyll fluorescence and antioxidant defense in two peach rootstocks differing in Fe deficiency tolerance. 1639 8

Cardiac function is depressed and circulating IL-6 levels increase following trauma-hemorrhage (T-H). Although sustained elevated IL-6 after T-H correlate with poor outcome, the mechanism by which IL-6 produces cardiac dysfunction remains unknown. We hypothesized that IL-6-mediated cardiac depression is due to upregulation of NF-small ka, CyrillicB, ICAM, CINC and neutrophil infiltration. Six groups of male adult rats (275-300 g) were used: sham/T-H + vehicle, sham/T-H + IgG, sham/T-H + anti-IL-6mAb. Following midline laparotomy, 60% of the circulating blood was withdrawn and after 90 min, crystalloid fluid resuscitation was provided. Either normal goat IgG or anti-rat IL-6mAb (16.7 microg/kg BW) was administered intraperitoneally at 30 min after the onset of resuscitation. Two hours after resuscitation, cardiac function was measured, blood samples collected, cardiomyocytes isolated and intracellular IL-6 levels measured by flow cytometry. Cardiac IL-6, IL-6R, gp130, NF-small ka, CyrillicB, Ismall ka, CyrillicB-alpha, and ICAM-1 protein levels were measured in freshly isolated hearts by immunoblotting. Moreover, cardiac MPO activity and CINC-1 and -3 were measured. Cardiac function was depressed and cardiac IL-6, NF-small ka, CyrillicB, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after T-H. Administration of anti-IL-6mAb following T-H: 1) improved cardiac output (P<0.05); 2) downregulated cardiac IL-6 levels (P<0.05); 3) attenuated cardiac NF-small ka, CyrillicB, ICAM-1, CINC-1, -3, and MPO activity (P<0.05). Administration of IgG, however, did not significantly influence these parameters. Thus, IL-6-mediated upregulation of cardiac NF-small ka, CyrillicB, ICAM-1, CINC-1, -3, and MPO activity likely contributes to altered cardiac function following T-H and neutralization of IL-6 therefore appears to be an effective and novel adjunct for improving organ/cell function under those conditions.
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PMID:Mechanism of IL-6-mediated cardiac dysfunction following trauma-hemorrhage. 1649 25

In this study, we have evaluated the effects of the polyphenol epigallocatechin-3-gallate (EGCG), an antioxidant molecule that also enhances constitutive nitric-oxide synthase (NOS) activity, on antigen-induced asthma-like reaction in sensitized guinea pigs. For comparison, we used epicatechin, which shares antioxidant but not NOS-modulating properties with EGCG. Ovalbumin-sensitized guinea pigs placed in a respiratory chamber were challenged with ovalbumin. EGCG (25 mg/kg b.wt.) or epicatechin (25 mg/kg b.wt.) was given i.p. 20 min before ovalbumin challenge. We analyzed latency time for the onset of respiratory abnormalities, cough severity, duration of dyspnea, lung tissue histopathology, mast cell activation (by granule release), leukocyte/eosinophilic infiltration (by major basic protein and myeloperoxidase), oxygen free radical-mediated injury (by nitrotyrosine and 8-hydroxy-2-deoxyguanosine and superoxide dismutase), NOS activity, and bronchial inflammatory response [by tumor necrosis factor-alpha in bronchoalveolar lavage (BAL)]. In the sensitized animals, severe respiratory abnormalities appeared soon after the antigen challenge, accompanied by bronchoconstriction, alveolar inflation, and a marked increase in the assayed parameters of inflammatory cell recruitment, free radical lung injury, and release of proinflammatory molecules in BAL fluid. This was associated with marked depression of constitutive NOS activity. Pretreatment with EGCG, but not epicatechin, significantly reduced all the above parameters and sustained endothelial-type NOS activity. These findings provide evidence that EGCG, probably by modulating NOS activity, can counteract allergic asthma-like reaction in sensitized guinea pigs and suggest its possible future use for the treatment of asthma.
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PMID:Epigallocatechin-3-gallate reduces allergen-induced asthma-like reaction in sensitized guinea pigs. 1652 38


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