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)

The role of insulin as a possible mediator of the beta-adrenergic agonist stimulation of muscle growth was investigated. To exclude possible action of the beta-agonist on the pancreatic release of insulin, diabetes was induced in rats by a streptozotocin injection (100 mg/kg). Insulin levels were almost not detectable in these rats. Feeding either normal diet or diet containing the beta-adrenergic agonist clenbuterol (10 parts/million) did not alter plasma insulin concentrations. The effects of clenbuterol on muscle and weight gain were determined in diabetic rats given daily insulin replacement (D + I) and fed either a normal diet or clenbuterol-treated diet. Clenbuterol, fed for 1 wk, increased the wet weight of the gastrocnemius, soleus, and extensor digitorum longus muscles (15-23%) in both normal and D + I rats. Although clenbuterol increased body weight gain, it did not alter feed consumption and, therefore, feed efficiency (g gain/g food) was improved. Activities of cathepsin B and N-acetyl-beta-glucosaminidase, but not cathepsin D, were elevated in the soleus muscles of clenbuterol-treated rats. The clenbuterol-induced increase in muscle growth in the insulin-replaced diabetic rats indicated that this beta-adrenergic agonist effect was not mediated by an alteration of circulating levels of insulin, secondary to beta-agonist action on pancreatic insulin release.
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PMID:Clenbuterol-induced muscle growth: investigation of possible mediation by insulin. 331 Jun 57

In order to obtain information about the changes in lysosomal enzyme activities in arterial endothelial cells under hypertensive conditions, a biochemical study was performed on 5 lysosomal enzymes, acid phosphatase, N-acetyl-beta-glucosaminidase (NAGase), cathepsin B, cathepsin D and beta-glucuronidase, in endothelial cells isolated by an enzymatic technique from the aorta of spontaneously and renal hypertensive rats, and normotensive control rats. The aortic endothelial cells in the old spontaneously and the renal hypertensive rats showed increased activities of enzymes examined in comparison with those in the age-matched control rats. Endothelial cells in young spontaneously hypertensive rats did not show any elevated enzyme activities compared with those in the controls, and the enzyme activities tended to increase with aging. From this, it is deduced that hypertension activates lysosomal enzyme activities in aortic endothelial cells. The differences in the activities of NAGase, cathepsin B and cathepsin D between hypertensive and control animals increased markedly with advancing age. These activated lysosomal enzymes seem to be involved in the developmental mechanism of arterial endothelial cell injury in hypertension and in further development of hypertensive vascular changes.
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PMID:Effect of hypertension on lysosomal enzyme activities in aortic endothelial cells. 335 16

The reported cytoprotective effects of prostaglandins against noxious stimuli in the liver was the basis for the present investigations of the effects of prostacyclin (PGI2) and a prostaglandin analogue (BW 245C) in an animal model of severe liver failure. Rats were given galactosamine at two dose levels and the prostaglandins were given in repeated doses from 0 to 6 h during the development of the liver damage or in another group from 24 to 30 h at the time of maximal liver injury. For PGI2 significant cytoprotection was found as assessed by a reduction in blood Normotest at 24, 48 and 72 h (P less than 0.05) and the plasma level of aspartate aminotransferase at 24 and 48 h (P less than 0.02) and the lysosomal markers N-acetyl-beta-glucosaminidase at 24, 48 and 72 h (P less than 0.001) and cathepsin D at 48 h (P less than 0.005) as compared to appropriate controls. Early administration of PGI2 reduced the mortality rate from 63% in the control group to 0% (P less than 0.01) in the treated group, but no significant effects were found when either compound was given later in the 24-h to 30-h period.
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PMID:Effect of prostacyclin (PGI2) and a prostaglandin analogue BW 245C on galactosamine-induced hepatic necrosis. 351 86

The development of a model of chronic myocardial ischemic injury (MII) in rabbits by administering increasing doses of isoproterenol (ISO) is described. Repeated s.c. injections of increasing doses of ISO (0.5 mg/kg, on day 1 to 15.5 mg/kg, on day 15) resulted in an increase in serum glucose, free fatty acids and creatine phosphokinase. Examination of hearts from ISO-treated rabbits revealed marked hypertrophy of the left ventricle and an increase in total water content. Biochemical analysis showed an increase in left ventricular hydroxyproline and a decrease in ATP and glycogen content following ISO-treatment. Ion measurements revealed extensive accumulation of Na and Ca, with the Ca being preferentially accumulated in the mitochondria. Measurement of subcellular organelle marker enzymes showed decreases in the sarcolemmal Na+-K+-stimulated (ouabain-sensitive), mitochondrial (azide-sensitive) and sarcoplasmic reticulum ATPase activities in the ISO-treated animals. Analysis of lysosomal enzyme activities in myocardial homogenates showed significant decreases in the latency of N-acetyl-beta-glucosaminidase and cathepsin D. The above biochemical alterations in ISO-induced MII generally parallel changes previously seen in the rabbit following acute coronary artery ligation. The present model allows the study of MII uncomplicated by some uncertainties arising from the surgical or anesthetic procedures employed in acute "open-chest" preparations and would permit long-term follow-up studies of pharmacological interventions. The susceptibility of the rabbit to experimental atherosclerosis should allow the development of an experimental model of MII which more closely approximates the clinical situation.
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PMID:Myocardial ischemic injury induced by isoproterenol in the rabbit: biochemical and chemical alterations. 385 Jul 74

Macrophages carry receptors on their surface for acetylated low density lipoprotein (ac-LDL). Receptor-mediated endocytosis of ac-LDL is followed by intracellular cholesterol accumulation. We investigated whether occupation of these binding sites evokes the release of hydrolytic enzymes from mouse peritoneal macrophages cultured for up to 48 h. ac-LDL at concentrations ranging from 25-250 micrograms protein/ml was noted to promote in a dose-dependent fashion secretion of the neutral proteinase elastase (EC 3.4.21.37) and the lysosomal acid hydrolases N-acetyl-beta-glucosaminidase (EC 3.2.1.30), beta-glucuronidase (EC 3.2.1.31), beta-galactosidase (EC 3.2.1.23), alpha-mannosidase (EC 3.2.1.24) and cathepsin D (EC 3.4.23.5). This stimulatory effect was non-cytotoxic. LDL modified by treatment with malondialdehyde was also capable of augmenting enzyme liberation into culture supernates. These findings may have implications for some aspects of the atherosclerotic process.
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PMID:Chemically modified low density lipoproteins as inducers of enzyme release from macrophages. 400 64

Homogenates of cultured rat embryo fibroblasts have been assayed for acid phosphatase, N-acetyl-beta-glucosaminidase, cathepsin D, acid deoxyribonuclease, cytochrome oxidase, NADH cytochrome c reductase, 5'-nucleotidase, inosine diphosphatase, acid pyrophosphatase, neutral pyrophosphatase, esterase, catalase, cholesterol, and RNA. The validity of the assay conditions was checked. Neutral pyrophosphatase is a readily soluble enzyme. Acid hydrolases, except acid pyrophosphatase, are particle-bound enzymes, which exhibit a high degree of structural latency. They are activated and solubilized in a parallel fashion by mechanical treatments and tensio-active agents. Catalase is also particle-bound and latent; activating conditions stronger than those for hydrolases are required to activate the enzyme. Acid pyrophosphatase, 5'-nucleotidase and inosine diphosphatase are firmly particle-bound, but not latent; they are not easily solubilized. In differential and isopycnic centrifugation, the latent hydrolases, cytochrome oxidase and catalase dissociate largely from each other; this suggests the occurrence of lysosomes and peroxisome-like structures besides mitochondria. The distribution patterns of 5'-nucleotidase and cholesterol are largely similar; digitonin influences their equilibrium density to the same extent; these two constituents are thought to be related to the plasma membrane. Inosine diphosphatase and acid pyrophosphatase are also partially associated with the plasma membrane, although some part of these enzymic activities probably belongs to other structures. NADH cytochrome c reductase is associated partly with the endoplasmic reticulum, partly with mitochondria.
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PMID:Analytical fractionation of homogenates from cultured rat embryo fibroblasts. 437 90

Homogenates of the posterior latissimus dorsi muscle, a phasic muscle, were fractionated by a one-step zonal centrifugation technique into four major organelle populations and cytoplasmic constituents. These were: (1) Plasma membrane fragments with a modal equilibrium density of 1.10 and containing 5'-nucleotidase, alkaline phosphodiesterase, p-nitrophenylphosphatase and acid phosphatase (beta-glycerophosphate was used as the substrate). (2) Sarcoplasmic reticular fragments which could be further subdivided into calcium transport vesicles, with a model equilibrium density of 1.16, that exhibited calcium uptake; K+-ATPase; leucyl-bet-naphthylamidase; acid phosphodiesterase; acid phosphatase (using cytidine monophosphate as the substrate); and sarcoplasmic reticular lysosomes, with a model equilibrium density of 1.18, possessing dipeptidyl-aminopeptidase II, cathepsin D, alpha-glucosidase, N-acetyl-beta-glucosaminidase, and NADH oxidase activity. (3) Mitochondria with a modal equilibrium density of 1.21. (4) Catalase-containing vesicles with a modal equilibrium density of 1.22; and cytoplasmic constituents (modal density of 1.25) with phosphorylase, pyruvate kinase, myosin-ATPase, aldolase, and protein and RNA content. The purity of these organelles was equal to or better than previous efforts, with a 30-fold purification achieved for 5'-nucleotidase and alkaline phosphodiesterase. These results lend support to the hypothesis that the sarcoplasmic reticulum of phasic muscle, in addition to its specialized role in excitation-contraction coupling, represents a multifunctional membrane system, and that, similar to the smooth endoplasmic reticulum of other cells, it includes some membrane-bound lysosomal enzymes and NADH oxidase.
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PMID:Isopycnic-zonal centrifugation of plasma membrane, sarcoplasmic reticular fragments, lysosomes, and cytoplasmic proteins from phasic skeletal muscle. 721 87

The retinal pigment epithelium (RPE) removes the outer segments of photoreceptor cells by phagocytosis. We studied the effects of tamoxifen and chloroquine on the activity of the lysosomal enzymes N-acetyl-beta-glucosaminidase and cathepsin D in RPE in vitro to evaluate the possible eye toxicity caused by these drugs. The results show decreases in the activities of lysosomal enzymes after drug exposure. The enzymes tested seemed to be more sensitive to tamoxifen than to chloroquine. A profound decrease in the activities of the lysosomal enzymes only started at concentrations above therapeutic dose levels.
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PMID:Retinal pigment epithelium cell culture as a model for evaluation of the toxicity of tamoxifen and chloroquine. 857 54

The cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells might contribute to atherosclerosis by causing cell death, presumably by both apoptosis and necrosis. After its uptake into macrophage lysosomes by receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in ceroid-containing foam cells. We studied the influence ofoxLDL on lysosomal enzyme activity and, in particular, on lysosomal membrane stability and the modulation of these cellular characteristics by HDL and vitamin E (vit-E). Unexposed cells and cells exposed to acetylated LDL (AcLDL) were used as controls. The lysosomal marker enzymes cathepsin L and N-acetyl-beta-glucosaminidase (NAbetaGase) were biochemically assayed in J-774 cells after fractionation. Lysosomal integrity in living cells was assayed by the acridine orange (AO) relocation test. Cathepsin D was immunocytochemically demonstrated in J-774 cells and human monocyte-derived macrophages. We found that the total activities of NAbetaGase and cathepsin L were significantly decreased, whereas their relative cytosolic activities were enhanced, after oxLDL exposure. Labilization of the lysosomal membranes was further proven by decreased lysosomal AO uptake and relocation to the cytosol of cathepsin D, as estimated by light and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The results indicate that endocytosed oxLDL not only partially inactivates lysosomal enzymes but also destabilizes the acidic vacuolar compartment, causing relocation of lysosomal enzymes to the cytosol. Exposure to AcLDL resulted in its uptake with enlargement of the lysosomal apparatus, but the stability of the lysosomal membranes was not changed.
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PMID:Uptake of oxidized LDL by macrophages results in partial lysosomal enzyme inactivation and relocation. 948 81

Retinal pigment epithelial cells carry out phagocytosis and digestion of material shed from the photoreceptor outer segments. In this process, the integrity of lysosomal enzymes is of major importance. In the present study the effects of tamoxifen, toremifene and chloroquine on the activity of two lysosomal enzymes (cathepsin D and N-acetyl-beta-D-glucosaminidase) in the retinal pigment epithelial cells were studied. Retinal pigment epithelial cells from pig eyes were cultured for two weeks in Dulbecco's Modified Eagle Medium, after which the cells were exposed to 1-40 microM concentrations of tamoxifen citrate, toremifene citrate and chloroquine diphosphate. To eliminate possible medium-borne oestrogenic mechanisms, the test was repeated using phenol red-free medium with charcoal-stripped fetal calf serum. The exposure time was one week, after which the lysosomal enzymes cathepsin D and N-acetyl-beta-glucosaminidase were determined. Cellular injuries were assessed by quantifying the leakage of lactate dehydrogenase into the culture medium. Cathepsin D and N-acetyl-beta-D-glucosaminidase showed different sensitivities to tamoxifen, toremifene and chloroquine. The main lysosomal protease cathepsin D was more sensitive than N-acetyl-beta-D-glucosaminidase to the effects of tamoxifen and toremifene, possibly due to their antioestrogenic properties. The phenol red-free medium with charcoal-stripped serum seemed to make the drugs more effective than the reference medium. Chloroquine had only a minor effect on the lysosomal protease cathepsin D, but a clearer effect could be seen on N-acetyl-beta-glucosaminidase.
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PMID:Effects of tamoxifen, toremifene and chloroquine on the lysosomal enzymes in cultured retinal pigment epithelial cells. 986 42


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