Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.23.5 (cathepsin D)
4,130 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

Cathepsin D of human leukocytes was isolated and characterized. Purified leukocytes were lysed under nitrogen pressure and the proteinase activity precipitated by centrifugation at 48,000 x g. The precipitate was extracted by various buffers. The yield of cathepsin D was almost pH-independent but could be increased by Triton X-100. Employing gel chromatography the activity was found at a molecular mass close to 42,000 Da. Purification of the enzyme was performed by a two-step procedure using pepstatin-Sepharose chromatography and ion exchange chromatography. Three multiple forms of the enzyme were separated by ion exchange chromatography. The isoelectric points of the three forms of the enzyme were close to pH 5.0. The enzyme showed the typical characteristics of the acid proteinase cathepsin D. Enzyme activity was influenced by heavy metals such as Hg2 and Fe3 as well as by typical inhibitors for carboxyl-proteinases such as diazoacetyl-DL-norleucine methyl ester, 1,2-epoxy-3-(4-nitrophenoxy)propane and 4-bromo-phenacylbromide. An immunological comparison with cathepsin D from human liver by immunodiffusion and immunoelectrophoresis indicates identity of the two enzymes.
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PMID:Cathepsin D from human leukocytes. Purification by affinity chromatography and properties of the enzyme. 314 53

Defibrotide stimulates PGI2 production and exerts significant antithrombotic, fibrinolytic and plasminogen-activating activities. We studied its effects in splanchnic artery occlusion (SAO) shock in rats. 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 90-120 minutes after releasing the clamps. Defibrotide 910 mg/kg +25 mg/kg/h) treated SAO shock rats maintained higher post-reperfusion mean arterial blood pressure compared to those receiving only the vehicle (0.9% NaCl). SAO shock rats treated with defibrotide exhibited lower plasma activities of the lysosomal protease cathepsin D (p less than 0.05 from vehicle) and myocardial depressant factor (p less than 0.02 from vehicle) as well as the plasma accumulation of free amino-nitrogen compounds (p less than 0.05 from vehicle). All SAO shock rats treated with defibrotide survived the entire 120 post-release period compared with only a 42% survival rate for rats receiving only the vehicle (p less than 0.02). These results suggest a remarkable protective effect of defibrotide in SAO shock.
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PMID:Beneficial mechanisms of action of a prostacyclin enhancing agent in splanchnic artery occlusion shock. 317 28

The role of platelet activating factor (PAF) in acute myocardial ischemia (MI), produced by the ligation of the left main coronary artery, was studied in anesthetized rats. A significant loss of cardiac amino-nitrogen concentration and cathepsin D activity was observed 6 hr after permanent occlusion MI or 10 min of MI followed by 6 hr of reperfusion in rats. A novel, potent, PAF antagonist, CV-6209 (160 nmol/kg or 1.6 mumol/kg) injected after the ligation, significantly retarded the loss of amino-nitrogen and cathepsin D activity in a dose-related manner. In another group of rats, CV-6209 (1.6 mumol/kg) significantly blocked the hypotension induced by repetitive injections of PAF (570 pmol/kg) with an apparent half-life of approximately 180 min. In isolated rat hearts perfused with Krebs-Henseleit solution, PAF (25 nmol/l) significantly increased coronary perfusion pressure by 15 +/- 2 mmHg and induced an increase in cardiac permeability using fluorescein isothiocyanate bovine albumin as a marker. Furthermore, the increase in cardiac permeability induced in isolated perfused rat hearts undergoing 15 min global ischemia followed by reperfusion was significantly attenuated by CV-6209 (250 nmol/l). These data indicate that PAF is an important mediator of ischemic damage in rat MI. Moreover, the extension of ischemic damage may be enhanced by the increase in cardiac permeability induced by PAF.
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PMID:Role of platelet activating factor in propagation of cardiac damage during myocardial ischemia. 325 36

Sporothrix schenckii, mainly in the yeast form of the organism, produced extracellular proteinases when cultivated in liquid media containing albumin or collagen as a nitrogen source, but did not do so in brain heart infusion medium. Isolation of two extracellular proteinases from albumin-containing medium was performed by chromatography on DEAE-Sepharose CL-6B and Sephacryl S-200. Proteinase I had a molecular weight of 36,500, an optimal pH at 6.0, and a pI at 4.8. Despite its activities in weakly acidic conditions, proteinase I demonstrated chymotrypsinlike characteristics, these being indicated by strong inhibitory activity by phenylmethylsulfonyl fluoride and chymostatin and good kinetic constants for a synthetic chymotrypsin substrate, Suc-Ala-Ala-Pro-Phe-MCA. Proteinase II had a molecular weight of 39,000, an optimal pH at 3.5, and a pI at 3.8. Proteinase II showed cathepsin D-like characteristics, these being indicated by strong inhibitory activity by pepstatin, an acidic optimal pH, and good kinetic constants for hemoglobin. These two enzymes hydrolyzed natural substrates such as stratum corneum, type I collagen, and elastin although not type IV collagen. Proteinase production and cell growth in collagen-containing medium and the enzymatic digestion of skin constituents by isolated proteinases suggested that these two proteinases cooperatively enable the organism to invade skin and to obtain peptides from insoluble proteins.
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PMID:Isolation and properties of extracellular proteinases from Sporothrix schenckii. 330 79

We studied the effects of prostaglandin E1 (PGE1) in a severe model of hemorrhagic shock in rats. PGE1 was administered as a continuous IV infusion of either 0.1 microgram/kg/min or 1.0 microgram/kg/min starting 30 minutes after the onset of bleeding and continuing until one hour after reinfusion. Hemorrhaged rats treated with PGE1 (1 microgram/kg/min) maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values than rats receiving only the vehicle (ie, 0.9% NaCl) (final MABP 84 +/- 3 vs 57 +/- 4 mm Hg, P less than .01). PGE1 at 1 microgram/kg/min also attenuated the increase in plasma activities of cathepsin D (P less than .01), and at both doses blunted the plasma accumulation of free amino-nitrogen compounds (P less than .02 at 0.1 microgram/kg/min and P less than .01 at 1.0 microgram/kg/min). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in rats treated with PGE1 (1 microgram/kg/min) than in rats receiving the vehicle (35 +/- 4 U/mL vs 74 +/- 12 U/mL, P less than .01). Rats receiving PGE1 (1.0 microgram/kg/min) also exhibited a significantly increased survival rate (P less than .01) and post-reinfusion survival time (P less than .01) compared with rats receiving only the vehicle. Our data suggest that antiproteolytic and membrane-stabilizing actions of PGE1 are important and may contribute to its beneficial effects in hemorrhagic shock. Other mechanisms (eg, inhibition of platelet aggregation and vasodilation) may also be involved.
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PMID:Mechanisms of action of PGE1 in hemorrhagic shock in rats. 336 25

The peptide leukotrienes are biologically active eicosanoids which have recently been implicated as possible mediators of anaphylactic, endotoxic, traumatic, and splanchnic artery occlusion shock. We studied the effects of a novel selective peptide leukotriene antagonist, L-649,923, in a rat model of hemorrhagic shock. Hemorrhaged rats treated with L-649,923 (1 mg/kg/h) maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values than rats receiving either 0.9% NaCl or a lower dose (0.2 mg/kg/h) of L-649,923 (final MABP 97 +/- 4 vs 60 +/- 5, p less than 0.01; vs 60 +/- 4 mm Hg, p less than 0.01, respectively). Both doses of L-649,923 attenuated the increase in plasma cathepsin D activity (p less than 0.01). L-649,923, at 1 mg/kg/h, also attenuated the plasma accumulation of free amino-nitrogen compounds (p less than 0.05). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in rats treated with L-649,923 (1 mg/kg/h) than in rats receiving the lower dose of the drug or the vehicle (36 +/- 5 U/ml vs. 61 +/- 4 U/ml, p less than 0.01; and 60 +/- 3 U/ml, p less than 0.01, respectively). Furthermore, L-649,923 does not inhibit platelet aggregation in platelet rich plasma. Our data suggest that peptide leukotrienes are important mediators of hemorrhagic shock and that blockade of leukotriene-induced vasoconstriction may underlie the beneficial effects of L-649,923 in hemorrhagic shock.
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PMID:Beneficial actions of antagonism of peptide leukotrienes in hemorrhagic shock. 338 53

We studied the effects of human superoxide dismutase (h-SOD) in splanchnic artery occlusion (SAO) shock. Pentobarbital anesthetized rats subjected to total occlusion of the superior mesenteric and the celiac arteries for 40 min developed a severe shock state usually resulting in a fatal outcome within 20 min after the release of the occlusion. h-SOD (10 mg/kg) was infused intravenously starting at reperfusion and lasting for 10 min. SAO shock rats treated with h-SOD maintained postreperfusion MABP at significantly higher values compared to rats receiving the vehicle (final MABP 84 +/- 6 vs 46 +/- 1 mm Hg, P less than 0.01, respectively). Treatment with h-SOD attenuated the plasma accumulation of free amino-nitrogen compounds (P less than 0.01 from vehicle) as well as the activity of the lysosomal protease cathepsin D (P less than 0.05 from vehicle). Furthermore, the plasma activity of a myocardial depressant factor was significantly lower in h-SOD-treated rats than in SAO rats receiving only the vehicle (27 +/- 1 vs 64 +/- 3 U/ml, P less than 0.01). SAO shock rats treated with h-SOD also exhibited a significantly higher survival rate than the SAO shock +/- vehicle group (88% vs 11%, P less than 0.01, respectively). These results support the role of oxygen-derived radicals in the pathophysiology of SAO shock, and indicate that h-SOD effectively ameliorates the deleterious effects of oxygen radicals in this severe model of ischemia and reperfusion.
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PMID:Anti-shock effects of human superoxide dismutase in splanchnic artery occlusion (SAO) shock. 339 43

We studied the effects of LY-163443, a novel selective receptor antagonist of LTD4 and LTE4, in splanchic artery occlusion (SAO) shock. LY-163443 antagonized the bronchoconstrictor effect of LTD4 given intravenously to anesthetized rats. Anesthetized rats subjected to total occlusion of the superior mesenteric and the celiac arteries for 40 minutes developed a severe shock state usually resulting in a fatal outcome within two hours after release of the occlusion. SAO shock rats pre-treated with LY-163443 before the occlusion of the splanchnic arteries maintained post-release MABP at significantly higher values compared to rats receiving either the vehicle or LY-163443 as a post-treatment 15 min after occlusion (final MABP 96 +/- 8 vs 51 +/- 1, p less than 0.01 and 53 +/- 3, p less than 0.01, respectively). Pre-treatment with LY-163443 attenuated the release of the lysosomal hydrolase, cathepsin D (p less than 0.01 from vehicle and p less than 0.05 from post-treatment groups), and the plasma accumulation of free amino-nitrogen compounds (p less than 0.05 from vehicle). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in the pre-treatment group than in the vehicle group (27 +/- 3 vs 51 +/- 6 U/ml, p less than 0.01). SAO shock rats pretreated with LY-163443 also exhibited significantly higher survival rates (p less than 0.01 from vehicle and post-treatment groups), and prolonged survival times (p less than 0.01 from vehicle and post-treatment groups).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Use of a novel peptide leukotriene receptor antagonist, Ly-163443, in splanchnic artery occlusion shock. 340 41

We studied the effects of a potent, specific platelet activating factor (PAF) antagonist, CV-6209, in a murine model of hemorrhagic shock. Hemorrhaged rats treated with CV-6209 (1 mg/kg) maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values than rats receiving either 0.9% NaCl or a lower dose (0.2 mg/kg) of CV-6209 (final MABP 88 +/- 4 vs. 57 +/- 4, vs. 61 +/- 7 mm Hg, respectively). CV-6209 (1 mg/kg) also significantly attenuated the increase in plasma cathepsin D activity following hemorrhage compared with hemorrhaged rats receiving only its vehicle (i.e. 0.9% NaCl). CV-6209 (1 mg/kg) also significantly decreased the plasma accumulation of free amino-nitrogen compounds and the plasma activity of a myocardial depressant factor (MDF) compared to hemorrhaged rats receiving 0.9% NaCl. Rats receiving CV-6209 (1 mg/kg) exhibited a significantly increased survival rate and survival time post-reinfusion compared to rats receiving only the vehicle. These data indicate that PAF is an important mediator of hemorrhagic shock in the rat and that PAF receptor antagonists may be useful in hemorrhagic shock states.
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PMID:Salutary consequences of blockade of platelet activating factor in hemorrhagic shock. 340 51


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