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

---

Query: EC:3.4.23.5 (cathepsin D)
4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of growth hormone in regulating protein turnover was examined in a perfused preparation of rat skeletal muscle. The perfused muscle maintained in vivo levels of ATP and creatine phosphate and exhibited constant rates of oxygen consumption and protein synthesis. Hypophysectomy reduced the rate of protein synthesis, the concentration of RNA, and the efficiency of protein synthesis in gastrocnemius muscle to 30, 46, and 66 percent of normal, respectively. In vivo treatment of hypophysectomized (hypox) rats with bovine growth hormone (250 microgram/day for 5 days) resulted in small increases in protein synthesis and RNA, whereas synthesis/RNA was returned to near normal. Elevation of ribosomal subunits in psoas muscle indicated an inhibition of peptide-chain initiation in hypox rats that was reversed by in vivo growth hormone treatment. Thus, hypox rats exhibited both a decreased capacity and a decreased efficiency of protein synthesis. Growth hormone replacement primarily increased efficiency of protein synthesis. The rate of protein degradation and the activity of cathepsin D in gastrocnemius muscle were decreased by hypophysectomy. Growth hormone treatment had no significant effect on degradation.
...
PMID:Protein turnover in rat skeletal muscle: effects of hypophysectomy and growth hormone. 62 46

The efficacy of the synthetic glucocorticoid, methylprednisolone, was examined in vitro using an isolated cat liver perfused with a blood-free medium. Addition of endotoxin (75 microgram/g tissue) to the perfusate did not change perfusion pressure or total oxygen consumption. However, cellular integrity was severely compromised as reflected by increases in perfusate lactate dehydrogenase and cathepsin D activities, increases in tissue lysosomal fragility, and enlargement and vacuolization of lysosomes. Addition of methylprednisolone (1 x 10(-3) M) to the perfusion medium prevented the endotoxin-induced changes in hepatocyte integrity. It is suggested that a major action of endotoxin in the liver is to increase lysosomal fragility, and the protective action of methylprednisolone appears to be related to its lysosomal stabilizing action. The potent anti-endotoxin action of glucocorticoids in vivo may be due in part to the stabilization of lysosomal membranes in tissues such as the liver.
...
PMID:Anti-endotoxin actions of methylprednisolone in the isolated perfused cat liver. 69 67

Splanchnic artery occlusion (SAO) of the celiac, superior mesenteric, and inferior mesenteric arteries for 2 hr, followed by a 2-hr reperfusion period in cats produces a severe form of circulatory shock characterized by endothelial dysfunction, increased lysosomal leakage, and severe hypotension resulting from release of proteases, oxygen-derived free radicals, and other humoral mediators into the circulation. Administration of 0.75 mg/kg/hr of C873754, a nitric oxide (NO) donor, 10 min prior to reperfusion, significantly attenuated the accumulation of plasma cathepsin D from 12 +/- 3 U/ml in the SAO + vehicle group to 5 +/- 1 U/ml (P < 0.05) in the C87-3754 treated SAO group. A similar attenuation of plasma myocardial depressant factor (MDF) activity was observed in the C87-3754 treated cats (P < 0.02). Administration of C87-3754 significantly increased short term (i.e., 2-hr) survival rate (P < 0.05, compared to the vehicle group). Moreover, C87-3754 attenuated the SAO shock induced decline in release of endothelium-derived relaxing factor (EDRF) from isolated superior mesenteric artery (SMA) rings stimulated by acetylcholine and A23187. Additionally, C87-3754 significantly decreased PMN adherence to the superior mesenteric venous endothelium in vitro. Thus, treatment with the NO donor, C87-3754 reduced the accumulation of humoral mediators into the plasma while significantly attenuating endothelial dysfunction and improving short term survival.
...
PMID:Antishock and endothelial protective actions of a NO donor in mesenteric ischemia and reperfusion. 129 85

On the model of burn shock in rats, the influence of antibodies to lysosomal enzymes has been studied in respect to the cathepsin D activity, oxygen regimen, acid-base equilibrium in blood, and animal survival. It has been shown that the antibodies inactivate the cathepsin D activity which is increased in burn shock. Because of the decreased cardiodepressant action of the lysosomal enzymes, the blood circulation improves, the manifestations of hypoxia and metabolic acidosis are attenuated. The results obtained confirm an important role of the lysosomal in the pathogenesis of bur, shock and permit one to consider its therapy using antibodies to the lysosomal enzymes to be promising.
...
PMID:[Effects of antibodies to lysosomal enzymes on the course of experimental burn shock]. 142 Dec 87

The cytoprotective effect of various copper(II) complexes on the gastric mucosa damage induced by acute intragastric administration of ethanol was investigated. For in vitro experiments, the following copper(II) complexes were tested: Cu(II)(L-Trp)(L-Phe), Cu(II)(L-Leu)Cu(II)(L-Leu-Leu)(L-Leu), Cu(II)(L-Phe-L-Leu), Cu(II)(Gly-His-Lys), and Cu(II)(cyHis)2(ClO4)2. Inorganic copper such as CuSO4 was also tested. The free radical generating system, acting for 2 hr on cardial and fundic mucosa scrapings or mucosal microsomes, was Fe++ (20 microM)/ascorbate (0.25 mM). We found a marked inhibition to 75% of lipid peroxidation in the range 10-100 mM, regardless of whether copper was given in complexed or inorganic form. The results suggest that nontoxic copper(II)-amino acid complexes are able to neutralize oxygen-derived free radicals. In addition, copper(II) complexes suppressed membrane lipid peroxidation when mucosa homogenates were exposed to t-butyl hydroperoxide (1-20 microM) plus Fe++ (50 microM). In vivo experiments on rat stomachs, pretreated p.o. by gavage either with Cu(II)(L-Trp)(L-Phe) as paradigmatic agent or with copper sulphate at equivalent doses in the range 3-30 mg/kg body weight showed a significant decrease (30 min after 95% ethanol administration) in the number and severity of mucosal hemorrhagic lesions. In the gastric mucosa scrapings of copper-treated rats after ethanol exposure, we found that malondialdehyde and conjugated diene levels were unchanged compared to those of untreated controls; five enzyme activities released from lysosomes were near control values. In isolated mucosal cells, whether or not pretreated with 200 microM solution of either Cu(II)(L-Trp)(L-Phe) or CuSO4, the release of cathepsin D activity was also unmodified. The results suggest that the cytoprotective effect of Cu(II) complexes against ethanol-induced mucosal lesions was not associated in vivo to lipid peroxidation.
...
PMID:Cytoprotective effect of copper(II) complexes against ethanol-induced damage to rat gastric mucosa. 161 1

Experiments were conducted on rats with massive prolonged blood loss to study the effect of immunoglobulins to lysosomal enzymes in combination with isotonic sodium chloride solution on the values of hemodynamics, oxygen regimen, and acid-base balance in the organism. Administration of antibodies to the lysosomal enzymes with an infusion medium leads to a decrease of cathepsin D activity to the initial level. Most probably, diminution of proteolysis is conducive to improvement of circulation. Inhibition of protease activity improves the permeability of vessels and thus facilitates an increase of the volume of circulating plasma, which may be judged from the authentic decrease of the hematocrit and hemoglobin. The oxygen budget and the acid-base balance in the organism are restored more fully. The use of immunoglobulins to lysosomal enzymes prolongs the animals' life.
...
PMID:[Immunoglobulin antibodies to lysosomal enzymes as a means of proteolysis inhibition in severe blood loss]. 188 5

Decreased oxygen delivery and cellular hypoxia are important factors in the pathophysiology of hemorrhagic shock. We studied the effects of 100% oxygen at 1 and 3 ATA (atmosphere absolute) in a severe model of hemorrhagic shock induced by bleeding 50% of the total blood volume in rats. Post-treatment with 100% oxygen at 1 and 3 ATA maintained mean arterial blood pressure (MABP) in hemorrhaged rats at significantly higher values compared to untreated controls (P less than 0.01 at 1 and 3 ATA). Treatment with oxygen attenuated the increase in plasma activities of the lysosomal hydrolase cathepsin D (P less than 0.05 at 1 ATA; P less than 0.01 at 3 ATA). Oxygen at 3 ATA also attenuated the plasma accumulation of free amino-nitrogen compounds (P less than 0.05). Furthermore, hyperoxia prevented the final increase in hematocrit (P less than 0.05 at 1 ATA; P less than 0.01 at 3 ATA). Hemorrhaged rats treated with oxygen also exhibited a significantly longer survival time (P less than 0.01 at both doses), and higher survival rates (50% at 1 ATA and 100% at 3 ATA; P less than 0.05 and P less than 0.01, respectively) than untreated shock rats. No significant effect on any of the above mentioned variables was found in hemorrhaged rats treated with 7% oxygen at 3 ATA (oxygen pressure 0.2 ATA), indicating that all salutary effects can be attributed to oxygen and not to the increased ambient pressure per se. Our results indicate that 100% oxygen in normobaric and hyperbaric conditions exerts important beneficial effects in hemorrhagic shock and may be a useful drug for the treatment of this condition.
...
PMID:Oxygen therapy in hemorrhagic shock. 204 10

During the acute experimental nephritis a decrease of reabsorption by proximal tubules is combined with the activation of the lipid peroxidation into the renal cortex without changes in the activation of lysosomal enzyme of acid phosphatase and cathepsin D. Ionol, an inhibitor of oxygen products, exerts a protective action on the renal function and reabsorption by proximal tubules, decreasing concentration of the malondialdehyde into the renal cortex.
...
PMID:[Pathogenetic significance of lipid peroxidation in damage of the proximal segment of the nephron in acute Masugi's nephritis]. 259 77

We studied the effects of hyperbaric oxygen in a severe model of circulatory shock induced by occlusion and reperfusion of major splanchnic arteries (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, resulting in a uniformly fatal outcome after release of the occlusion. Exposure to hyperbaric oxygen at 2 ATA (atmosphere absolute) (1 ATA = 0.1 MPa) was initiated immediately after reperfusion. SAO shock rats exposed to hyperbaric oxygen maintained mean arterial blood pressure at significantly higher values throughout the postreperfusion period compared with untreated SAO shock rats (p less than 0.01), with final mean arterial blood pressures of 88 +/- 9 and 51 +/- 4 mmHg, respectively. Treatment with hyperbaric oxygen attenuated the increase in plasma activities of the lysosomal hydrolase cathepsin D (p less than 0.05), and diminished the increase of hematocrit (p less than 0.01 from untreated shock rats). Splanchnic occlusion shock rats treated with hyperbaric oxygen also exhibited a significantly higher survival rate than the untreated shock group (77 vs. 0%, respectively; p less than 0.01). Our results suggest that the beneficial effects of exposure to hyperbaric oxygen immediately after reperfusion of the splanchnic region outweigh its possible deleterious effect.
...
PMID:Effects of hyperbaric oxygen in circulatory shock induced by splanchnic artery occlusion and reperfusion in rats. 259 28

We investigated the effect of exogenous oxygen free radicals and various pH on the release of lysosomal hydrolases from dog myocardial lysosomes. A lysosomal enriched fraction from the homogenate of dog heart was prepared, using differential centrifugation technique. Exogenous oxygen free radicals were generated using xanthine-xanthine oxidase system. The release of lysosomal hydrolases was measured from the lysosomal enriched fraction. There was about 3-fold increase in the release of cathepsin D and beta-N-acetylglucosaminidase activities in the preparations treated with xanthine-xanthine oxidase as compared to those without such treatment. The presence of superoxide dismutase, an oxygen free radical scavenger, prevented the release of cathepsin D and beta-N-acetylglucosaminidase from the lysosomes. Sonication and lubrol treatments, which are known to cause membrane disruption, also induced the release of these enzymes from lysosomal enriched fraction. However, this release was not prevented by superoxide dismutase. The changes in pH (4.5, 5.5, 6.0, 6.5, 7.4, 8.0) alone did not cause any increase in the enzyme release. The presence of oxygen free radicals at each pH resulted in a similar increase in the release of cathepsin D and beta-N-acetylglucosaminidase. These studies suggest that oxygen free radicals and not the alterations in pH are primarily responsible for the release of lysosomal hydrolases. Oxygen free radicals, in addition to their direct myocardial damaging effect, may also be responsible for the cardiac damage through the release of lysosomal enzymes.
...
PMID:Role of oxygen free radicals and pH on the release of cardiac lysosomal enzymes. 260 45


1 2 3 4 5 6 7 8 9 10 Next >>

---