Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since prostaglandin E1 (PGE1) is known to have a beneficial effect in hemorrhagic shock, a biologically active derivative of PGE1, 6-keto-PGE1, was examined for its effect on traumatic shock in rats. In sham-operated rats, infusion of 6-keto-PGE1, at a rate of 250 ng/kg/min intravenously decreased arterial blood pressure by 23 mm Hg at 5 hr. In rats subjected to Noble-Collip drum trauma, infusion of 6-keto-PGE1, starting 15 min after the trauma, significantly improved the survival time from 1.0 +/- 0.1 to 2.6 +/- 0.3 hr compared to rats given only the vehicle (i.e., Tris buffer). The improved survival was accompanied by a diminished plasma accumulation of the cardiotoxic peptide, myocardial depressant factor (MDF), and the lysosomal protease cathepsin D. 6-keto-PGE1 also exerted a direct lysosomal stabilizing effect in isolated cat liver lysosomes, as well as reducing cardiac afterload in rats. It is concluded that 6-keto-PGE1 protects in traumatic shock by hemodynamic as well as cytoprotective actions.
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PMID:Protective action of 6-keto-prostaglandin E1 in traumatic shock. 57 62

The change of liver lysosomal enzymes in tissue and serum during a reperfusion period was studied in partial liver ischemic model in rats and effect of Prostaglandin E1 (PGE1) derivative on partial liver ischemia was investigated. Partial liver ischemia was induced by clamping the branches of the vessels to the right and caudate lobes of rat liver. The clamp was released after 30 minutes of ischemia. Ischemic and nonischemic lobes of the liver were separately removed and the serum was also collected immediately and two hours after the release of the clamp. Lysosomal enzyme activities from free and bound lysosomal fraction were measured separately and the fragility index (F.I.) was calculated. PGE1 derivative was administered intraperitoneally 24, 6, 0.5 hours prior to the induction of ischemia at each dose of 0.05 microgram/kg. Pretreatment with PGE1 derivative prevented lysosomal labilization in ischemic lobe, since there was a significant decrease in F.I. of cathepsin D in the PGE1-pretreated group (preischemia; 28.3 +/- 2.4%, immediately after reperfusion; 30.3 +/- 2.5%, two hours after reperfusion; 30.3 +/- 2.5%) compared to the placebo group (immediately after reperfusion; 40.9 +/- 3.4%, two hours after reperfusion; 41.7 +/- 3.4%, p less than 0.05, p less than 0.05, p less than 0.01, respectively). Pretreatment with PGE1 derivative also significantly suppressed the increase of serum lysosomal enzyme activity. These results showed that PGE1 derivative improved liver lysosomal labilization in partial liver ischemia.
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PMID:[Effect of prostaglandin E1 derivative on labilization of liver lysosomal membrane in partial liver ischemia]. 151 9

We have investigated the role of platelet activating factor (PAF) in the pathogenesis of a murine model of traumatic shock using CV-6209, a specific antagonist of PAF. CV-6209, at a dose of 1 mg/kg (i.v.) given after trauma, significantly improved survival rate at 150 min and overall survival time. Furthermore, the plasma accumulation of the lysosomal hydrolase, cathepsin D, and a cardiotoxic peptide, myocardial depressant factor (MDF), were also attenuated by CV-6209 in traumatic shock. Combined treatment employing low doses of CV-6209 [0.2 mg/kg, i.v. and prostaglandin (PG) E1, 0.8 microgram/kg/min] in this shock model was also examined. CV-6209 (0.2 mg/kg) or PGE1 (0.8 microgram/kg/min) alone at these doses showed only minimal effects on survival, or plasma cathepsin D or MDF activities. However, combined treatment with CV-6209 (0.2 mg/kg, i.v.) and PGE1 (0.8 microgram/kg/min) significantly improved survival rate at 150 min, overall survival time, and decreased the accumulation of plasma MDF. These results suggest that PAF may play an important pathophysiologic role in traumatic shock in rats. Moreover, combination therapy using a PAF antagonist and PGE1 may be useful for the treatment of traumatic shock.
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PMID:Protective effects of a platelet activating factor (PAF) antagonist and its combined treatment with prostaglandin (PG) E1 in traumatic shock. 246 48

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 effects of prostaglandin E1 (PGE1) were studied in a standardized model of traumatic shock in rats. Pentobarbital anesthetized rats were subjected to standardized drum trauma of 525 revolutions in a Noble-Collip drum. These traumatized rats were characterized by a survival time of 108 +/- 19 min, a 12-fold increase in plasma cathepsin D activity, and a three-fold increase in plasma myocardial depressant factor (MDF) activity. PGE1 (1.2 micrograms/kg X min) significantly improved survival time during traumatic shock (191 +/- 29 vs. 108 +/- 19 min), drug vs. vehicle, respectively (p less than .03). In addition, PGE1 significantly attenuated plasma MDF activity during traumatic shock (58 +/- 10 vs. 27 +/- 7 U/ml), vehicle vs. drug, respectively (p less than .02). Plasma cathepsin D activity was also significantly retarded (12.1 +/- 1.8 vs. 1.70 +/- 1.50 U/ml), vehicle vs. drug, respectively (p less than .01). PGE1 appears to exert a membrane stabilizing effect, decreasing plasma cathepsin D and attenuating MDF production. PGE1 thus appears to have significant antishock activity.
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PMID:Beneficial effects of prostaglandin E1 infusion in experimental traumatic shock. 360 33