UMLS:C0011570 - FACTA Search

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)

We studied RO 15-1788, a new benzodiazepine receptor antagonist, [ethyl 8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo (1, 5a) (1, 4) benzodiazepine-3-carboxylate] to determine its effects in a murine model of hemorrhagic shock. Hemorrhaged rats treated with RO 15-1788 maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values compared to rats receiving only the vehicle (final MABP 114 +/- 4 vs 82 +/- 4 mmHg, p less than 0.001). Moreover, RO 15-1788 decreased the release of the lysosomal hydrolase, cathepsin D (p less than 0.02) into the circulation and blunted the plasma accumulation of free amino-nitrogen groups (p less than 0.01). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in RO 15-1788 treated rats subjected to hemorrhagic shock than in those given the vehicle (18 +/- 2 vs 42 +/- 4 U/ml, p less than 0.01). Additionally, in vitro analysis indicated that RO 15-1788 antagonizes PAF induced coronary vasoconstriction and cardiac depression observed in perfused rat hearts, as well as inhibiting PAF induced platelet aggregation in cat platelet rich plasma. Our results suggest that antagonism of PAF actions can contribute significantly to the beneficial effects of RO 15-1788 in hemorrhagic shock.
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PMID:Beneficial actions of RO 15-1788, a benzodiazepine receptor antagonist, in hemorrhagic shock. 311 57

Splanchnic artery occlusion (SAO) followed by release of the occlusive clamps produces circulatory shock characterized by an abrupt hypotension, cardiac depression and high lethality. We studied the effects of the thromboxane receptor antagonist, BM-13505, in rats during SAO shock. Anesthetized rats subjected to total occlusion of the celiac and superior mesenteric arteries for 40 minutes developed a severe shock state following reperfusion, usually resulting in death within 90-120 minutes of release of the occlusion. BM-13505 was started at reperfusion for 10 minutes. SAO shock rats treated with BM-13505 (1 mg/kg) maintained post-reperfusion mean arterial blood pressure (MABP) at significantly higher values compared to those receiving only the vehicle (0.9% NaCl). Treatment with BM-13505 attenuated the plasma activity of the lysosomal protease cathepsin D (p less than 0.05 from vehicle) and the plasma accumulation of free amino-nitrogen compounds (p less than 0.01 from vehicle). Furthermore, the plasma activity of a myocardial depressant factor was significantly lower in BM-13505 treated rats than in non-treated rats (p less than 0.01 from vehicle). SAO shock rats treated with BM-13505 also exhibited a higher survival rate than the vehicle group (75% vs. 20%). These results suggest an important role of thromboxane A2 in the pathophysiology of SAO shock.
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PMID:Protective effects of thromboxane receptor blockade in splanchnic artery occlusion shock. 341 44

The effect of intensive physical exercise (swimming for 3 hours with a load of 4% body weight) on the function of hepatic, pulmonary and peritoneal macrophages has been studied in rats and mice. NBT values in alveolar and peritoneal macrophages of the experimental animals proved to be 1.5 and 1.6 times higher than in the controls. The activity of cathepsin D in the liver, lung and Kupffer cells was greater than the control values. The data obtained indicate that intensive physical exercise caused depression in phagocytic activity of Kupffer cells, the major compartment of the reticuloendothelial system, whereas a similar function in lung macrophages was even greater than in the controls and in peritoneal macrophages changed but insignificantly.
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PMID:[Functional rearrangements in macrophages following intensive physical exercise]. 362 Jun 85

Lysosomal enzyme activities in pancreatic islets of obese hyperglycemic ob/ob mice aged 3 to 6 months were investigated and compared with those of normal lean NMRI mice of the same age. It was observed that the glycogenolytic glucose-producing hydrolase acid amyloglucosidase displayed a fivefold higher activity in the islets of obese mice than in the islets of normal NMRI mice. However, other islet lysosomal enzyme activities measured, such as N-acetyl-beta-D-glucosaminidase and beta-glucuronidase, were of the same magnitude in both obese and lean mice. A starvation period of 24 hours induced a significant depression of islet acid amyloglucosidase activity in obese as well as lean mice, whereas the activities of N-acetyl-beta-D-glucosaminidase and beta-glucuronidase were unaffected. Further, the activities of other types of islet lysosomal enzymes, such as acid phosphatase and cathepsin D, were also measured in obese mice. These activities were not found to be affected by the actual fasting period. A good correlation (r = 0.815; P less than 0.01) was observed between islet acid amyloglucosidase activity and plasma insulin concentrations in obese mice, whereas no such relationship was apparent with regard to other islet lysosomal enzyme activities recorded. Acid amyloglucosidase activity in liver tissue of the obese mouse was about 30 times lower than that of islet tissue. Further, the activity of liver amyloglucosidase was of the same order of magnitude in obese and lean mice. Similarly, other lysosomal enzyme activities in the liver of obese and lean mice were not strikingly different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysosomal enzyme activities in pancreatic islets from normal and obese hyperglycemic mice. 391 27

Incubation of cultured hippocampal slices with chloroquine, a compound that increases the pH of acidic subcellular organelles, for 10 h reduced the activity of cathepsin L by 83 +/- 0.87% (mean +/- s.e.m.) while only marginally suppressing cathepsin B. This effect was followed within 3 h by an increase in the concentration of mature, single-chain cathepsin D (up 61 +/- 28%). Selective depression of cathepsin L with N-CBZ-L-phenylalanyl-L-phenylalanine-diazomethylketone also resulted in increases in enzymatically active cathepsin D and the delayed appearance of a 29 kDa fragment of the tau protein. These findings demonstrate that the pattern of cathepsin L, B, and D changes found in the aged brain can be reproduced by reducing the acidity of the lysosomal milieu. They also indicate that such pH shifts initiate a sequence of linked disturbances (inactivation of cathepsin L > induction of cathepsin D > aberrant tau proteolysis) likely to play an important role in brain ageing.
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PMID:Selective suppression of cathepsin L results from elevations in lysosomal pH and is followed by proteolysis of tau protein. 967 99

The endosomal lysosomal system might play a role in Alzheimer's disease, but its impact in major depression is unknown. The expression of the cation-dependent mannose 6-phosphate receptor (CD-MPR) is increased in Alzheimer's disease and the CD-MPR gene is located next to a region on chromosome 12 possibly linked to Alzheimer's disease. We investigated a C/T polymorphism in the CD-MPR gene in 188 Alzheimer's disease patients, in a control sample of 193 patients with major depression, as hospitalized controls, and in 259 healthy controls. We examined the interaction of the CD-MPR polymorphism with the putative risk factor for Alzheimer's disease, the cathepsin D T-allele. No significant association of the CD-MPR C-allele with Alzheimer's disease was observed. However, exploratory data analysis revealed an increased frequency of the CD-MPR C-allele in patients with major depression; thus, the C-allele may be a risk factor for depression. Gene location and function of the CD-MPR suggest an involvement in Alzheimer's disease; however, we could not find an association of the CD-MPR polymorphism with Alzheimer's disease. Since exploratory data suggest an involvement of the endosomal lysosomal system in major depression, further studies are warranted to investigate the biological role of the CD-MPR in major depression.
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PMID:Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer's disease. 1516 96

Induction of hypoxia for 2.5 h in perfused cat livers resulted in a 10-fold increase in cathepsin D and a 15-fold increase in lactic dehydrogenase (LDH) activities in the perfusate and a 42% depression of the clearance rate of particles by the reticuloendothelial system (RES). Addition of 10(-3) M methylprednisolone (MP) to the perfusate only slightly retarded the release of LDH, but significantly (P<0.05) inhibited cathepsin D release by 90% at 150 min. Liver flow did not change during the perfusion period when MP was added to control or hypoxic livers. Similarly, MP did not significantly alter oxygen consumption in perfused livers. However, MP protected against the reduction in carbon clearance during hypoxia without inducing blockade of colloidal carbon clearance. Moreover, opsonization of carbon with autologous plasma did not improve the clearance of colloidal carbon above that observed in nonopsonized experiments. Thus, pharmacologic doses of a synthetic glucocorticoid protected RES cells and release of lysosomal hydrolases during severe hypoxia in isolated perfused cat livers probably by stabilization of cellular and intracellular (lysosomal) membranes.
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PMID:Protection of hypoxic cytotoxicity by glucocorticoid in the liver. 2419 60

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1-TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.
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PMID:High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression. 2714 67

Several lines of evidence indicate that adverse experience in early life may be a triggering factor for disturbances in the brain mitochondrial proteins and lead to the development of depression in adulthood. On the other hand, little is known about the impact of chronic administration of various antidepressant drugs on the brain mitochondria, as a target for the pharmacotherapy of depression. The purpose of our study was to compare the impact of chronic treatment with two antidepressant drugs with different mechanisms of action, a tricyclic antidepressant (TCA), imipramine, and an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, fluoxetine, on the mitochondria-enriched subproteome profile in the hippocampus of 3-month-old male rats following a prenatal stress procedure (an animal model of depression). We clearly confirmed that chronic imipramine and fluoxetine administration not only normalized depression-like disturbances evoked by the prenatal stress procedure but also modulated the mitochondria-enriched subproteome profile in the hippocampus of adult offspring rats. In line with this, two-dimensional electrophoresis coupled with mass spectrometry showed a statistically significant down-regulation of 14-3-3 and cytochrome bc1 proteins and an up-regulation of COP9 signalosome expression after chronic imipramine treatment in the hippocampus of prenatally stressed offspring. Fluoxetine administration strongly up-regulated the expression of cathepsin D, one of the key proteins involved in the prevention of the development of neurodegenerative processes. Furthermore, this antidepressant treatment enhanced expression of proteins engaged in the improvement of learning and memory processes (STMN1, Dnm-1) as well as in mitochondrial biogenesis and defense against oxidative stress (DJ-1). These findings provide new evidence that chronic administration of antidepressants exerts a varied impact on the mitochondria-enriched subproteome in the hippocampus of adult rats following a prenatal stress procedure. In particular, the effect of fluoxetine requires additional experiments to elucidate the possible beneficial biological consequences underlying the effects mediated by this antidepressant.
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PMID:Evaluation of the effectiveness of chronic antidepressant drug treatments in the hippocampal mitochondria - A proteomic study in an animal model of depression. 2852 99

The first reported human anaphylactic death is considered to be the Pharaoh Menes death, caused by a wasp sting. Currently, anaphylactic cardiovascular events represent one of most frequent medical emergencies. Rapid diagnosis, prompt and appropriate treatment can be life saving. The main concept beyond anaphylaxis lies to myocardial damage and ventricular dysfunction, thus resulting in cardiovascular collapse. Cardiac output depression due to coronary hypoperfusion from systemic vasodilation, leakage of plasma and volume loss due to increased vascular permeability, as well as reduced venous return, are regarded as the main causes of cardiovascular collapse. Clinical reports and experiments indicate that the human heart, in general, and the coronary arteries, in particular, could be the primary target of the released anaphylactic mediators. Coronary vasoconstriction and thrombosis induced by the released mediators namely histamine, chymase, tryptase, cathepsin D, leukotrienes, thromboxane and platelet activating factor (PAF) can result to further myocardial damage and anaphylaxis associated acute coronary syndrome, the so-called Kounis syndrome. Kounis syndrome with increase of cardiac troponin and other cardiac biomarkers, can progress to heart failure and cardiovascular collapse. In experimental anaphylaxis, cardiac reactions caused by the intracardiac histamine and release of other anaphylactic mediators are followed by secondary cardiovascular reactions, such as cardiac arrhythmias, atrioventricular block, acute myocardial ischemia, decrease in coronary blood flow and cardiac output, cerebral blood flow, left ventricular developed pressure (LVdp/dtmax) as well as increase in portal venous and coronary vascular resistance denoting vascular spasm. Clinically, some patients with anaphylactic myocardial infarction respond satisfactorily to appropriate interventional and medical therapy, while anti-allergic treatment with antihistamines, corticosteroids and fluid replacement might be ineffective. Therefore, differentiating the decrease of cardiac output due to myocardial tissue hypoperfusion from systemic vasodilation and leakage of plasma, from myocardial tissue due to coronary vasoconstriction and thrombosis might be challenging during anaphylactic cardiac collapse. Combined antiallergic, anti-ischemic and antithrombotic treatment seems currently beneficial. Simultaneous measurements of peripheral arterial resistance and coronary blood flow with newer diagnostic techniques including cardiac magnetic resonance imaging (MRI) and myocardial scintigraphy may help elucidating the pathophysiology of anaphylactic cardiovascular collapse, thus rendering treatment more rapid and effective.
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PMID:Anaphylactic cardiovascular collapse and Kounis syndrome: systemic vasodilation or coronary vasoconstriction? 3030 71

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