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)

Renin-like activity in the heart and aorta of rats being slightly modified by binephrectomy, its variations in DOCA hypertension and infarcted ventricular muscle were studied. The daily i.p. administration of DOCA 12 mg/kg body weight for 35 days in male adult rats resulted in a significant decrease of renin activity in plasma and tissues of the heart, aorta, hypothalamus and hypophysis. In contrast to renin-like activity, cathepsin D measured in the same animals increased in all organs, except for the plasma. Similar changes of renin-like activity were observed in salt-loaded animals with 1.7% sodium chloride solution ad libitum for 35 days. In the infarcted myocardial ventricular muscle of the rats and rabbits, the tissue isorenin showed a tendency to decrease, associated with a significant increase in cathepsin D activity. Like in aorta, isorenin seems to be a different enzymatic entity of cathepsin D in the myocardial tissue. The measurement of isorenin content of the vascular endothelium and cardiac muscle fibers seems to reveal much higher amounts in the coronary vascular endothelium than in the myocardial fibres. The activation of the enzymatic angiotensin forming mechanisms in the coronary vascular bed could be one of the risk factors in myocardial infarction.
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PMID:A comparative study of the renin-like activity in the heart and vascular system under various experimental conditions. 642 49

The molecular charge of the macromolecule, horseradish peroxidase (HRPase, 40 000 mol. wt), was modified to yield highly anionic (PI less than 3.68) and cationic (PI = 9.5-10.5) derivatives. The effects upon the interactions between HRPase and arterial endothelium were then studied in vitro. The net rate of uptake of HRPase into endocytic vesicles and vacuoles of confluent endothelium was influenced by its molecular charge, there being less internalization of the anionic HRPase than of the native (pI = 7.9-8.2) and cationic derivatives. The molecular diameter was not significantly different between the cationic (Ae = 28.8 A), anionic (Ae = 31.2 A) and native (Ae = 29.6 A) HRPase. The rate of uptake of [U-14C]sucrose, a tracer of bulk fluid endocytosis, was unaffected by the presence of the differently charged HRPase, indicating that the volume of vesicles formed per cell per hour remained constant. The intracellular fate of HRPase of different charge was investigated biochemically and morphologically. The rate of loss of internalized HRPase activity in the endothelial cells approximated first-order kinetics. The rate of disappearance of intracellular HRPase activity was much greater for cationic (t1/2 = 8 h) and native (t1/2 = I 8 h) than for anionic HRPase (t1/2 = 80-100 h). By electron microscopy, all 3 forms of HRPase were restricted to intracellular membrane-bounded vesicles and vacuoles consistent with a vesicle-lysosomal pathway. Studies with purified lysosomal cathepsin D indicated that the differences in the intracellular half-lives of HRPase may be attributable in small part to decreased and increased rates of lysosomal proteolysis of anionic and cationic HRPase, respectively, in comparison with native HRPase. Pre-labelling of endothelial secondary lysosomes by inhibitors of phagosome-lysosome fusion (dextran sulphate, polyglutamate) lengthened the intracellular half-life of native HRPase, while introduction of cationic ferritin to cells pulsed with anionic HRPase greatly decreased its half-life. Thus an influence of molecular charge upon endosome-lysosome fusion cannot be excluded. The studies indicate that the net charge carried by exogenous HRPase influences both its internalization in endocytic vesicles and its subsequent intracellular fate, which in turn may be modified by the introduction of other differently charged macromolecules. These results are discussed in relation to macromolecular transport by vascular endothelium in vivo.
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PMID:Influence of molecular charge upon the endocytosis and intracellular fate of peroxidase activity in cultured arterial endothelium. 730 13

The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear particle-induced and septic loosening and to gather new insights into the pathogenesis of endoprosthesis loosening. Gene expression profiles were generated from five periprosthetic membranes of wear particle-induced and five of infectious (septic) type using Affymetrix HG U133A oligonucleotide microarrays. The results of selected differentially expressed genes were validated by RT-PCR (n = 30). The enzyme activity and the genotype of chitinase-1 were assessed in serum samples from 313 consecutive patients hospitalized for endoprosthesis loosening (n = 54) or for other reasons, serving as control subjects (n = 259). Eight hundred twenty-four genes were differentially expressed with a fold change greater than 2 (data sets on http://www.ncbi.nlm.nih.gov/geo/ GSE 7103). Among these were chitinase 1, CD52, calpain 3, apolipoprotein, CD18, lysyl oxidase, cathepsin D, E-cadherin, VE-cadherin, nidogen, angiopoietin 1, and thrombospondin 2. Their differential expression levels were validated by RT-PCR. The chitinase activity was significantly higher in the blood from patients with wear particle-induced prosthesis loosening (p = 0.001). However, chitinase activity as a marker for early diagnosis has a specificity of 83% and a sensitivity of 52%, due to a high variability both in the disease and in the control group.
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PMID:Gene expression in endoprosthesis loosening: chitinase activity for early diagnosis? 1790 71