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)

Extracts of rheumatoid synovial tissue obtained at surgical synovectomy contained neutral proteinases as well as cathepsin D. The neutral proteinase activity was particle-bound but could be solubilized by 1 M MgCl2. About half of the solubilized activity adsorbed to aproptinin-Sepharose at pH 7.5 and was desorbed at pH 3.3. This activity was shown to be due to leukocyte elastase and cathepsin G by enzymological and immunological criteria. The neutral proteinase activity that did not adsorb to aprotinin-Sepharose was not due to elastase or cathepsin G. It was able to hydrolyse proteoglycan and was inhibited by diisopropylfluorophosphate, soybean and lima bean trypsin inhibitors. It was, therefore, a serine proteinase. Its inhibition characteristics were different from those of plasmin, kallikrein or thrombin. All of the neutral proteinase activity of synovial extracts was attributable to serine proteinases, no evidence of metallo-proteinases was found. The possible role of the neutral proteinases in the degradation of the matrix of cartilage is discussed. A simple procedure for purifying leukocyte elastase and cathepsin G is described as well as the raising of specific antisera to these enzymes.
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PMID:Identification of proteinases in rheumatoid synovium. Detection of leukocyte elastase cathepsin G and another serine proteinase. 615 6

The enzymatic degradation of insoluble elastin has been studied at several pH values using purified pepsin and cathepsin D, and neutrophil extracts. Pepsin degraded elastin throughout the pH range of 1.2-4.0 with the optimum pH below 2.0. Molecular sieve chromatography and gel electrophoresis indicated that a spectrum of molecular weight degradation products was produced. The degradation by pepsin was inhibited by sodium dodecyl sulfate (SDS), NaCl and pepstatin. Cathepsin D, which, like pepsin, degrades hemoglobin at acid pH and is inhibited by pepstatin, had no activity against insoluble elastin in the pH range of 3.2-7.2. Extracts of neutrophils degraded elastin above pH 4.0. The pH profile of elastin degradation by neutrophil extracts generally followed that of purified human leukocyte elastase. Our results suggest that during alimentation or pulmonary aspiration of gastric contents, extracellular elastin may be digested by gastric juice at acid pH. Inflammatory cells would not appear to be capable of contributing to such actions until local pH approaches neutrality. Cathepsin D, a major constituent of inflammatory cells, does not digest all types of connective tissue proteins.
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PMID:The enzymatic digestion of elastin at acidic pH. 678 96

An apparatus and test method were developed to determine the elastic stiffness and damping coefficient of human cartilage in compression. An underdamped, counterbalanced beam applied a sudden compressive force to a full-thickness cylindrical specimen of articular cartilage. The initial oscillatory response decayed to steady state creep after approximately 10 cycles of oscillation. The results were consistent with a Voigt phenomenological model with linear stiffness and damping terms. Standard dynamics analysis of the transient oscillatory response enabled the elastic stiffness to be determined from the frequency and the damping coefficient to be derived from the logarithmic decrement of the decay of the oscillations. The relationship between the mechanical properties and structure of cartilage was determined by treating specimens with two specific proteolytic enzymes. Digestion and removal of proteoglycans alone with cathepsin D caused the damping coefficient to decrease with no change in elastic stiffness. The action of leukocyte elastase on collagen caused a decrease in both damping coefficient and elastic stiffness. It was concluded that the collagen fibrils in cartilage largely control the elastic response while the viscous response is controlled largely by the hydrated proteoglycans. The effects of cartilage thickness was also examined and found to be inversely proportional to the elastic stiffness. It is suggested that this method could be used to uncouple elastic and viscous properties of other viscoelastic materials.
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PMID:The short-term compressive properties of adult human articular cartilage. 795 Aug 72

The beta isoforms of protein Kinase C (PKC) are closely involved in the regulation of cell protein transport and secretion. We have shown in different cellular types that treatment with HNE in a concentration range detectable in many pathophysiological conditions is able to induce selective activation of betaPKCs through direct interaction between the aldehyde and these isoenzymes. In isolated rat hepatocytes this specific isoenzyme activation plays a key role in the transport of procathepsin D from the trans-Golgi network to the endosomal-lysosomal compartment and in the exocytosis of mature cathepsin D. In NT2 neurons, HNE-mediated betaPKC activation induces an increase in intracellular amyloid beta production, without affecting full-length amyloid precursor protein expression. In a mouse macrophage-like cell line, the same beta isoform activation increases the release of the MCP-1 chemokine. Thus, pathophysiological HNE concentrations (0.1-1 microM) derived from a slight imbalance of the redox state are able to alter protein trafficking through beta PKC activation. These results suggest that mild oxidative stress and the PKC signal transduction pathway are closely involved in the pathophysiology of many diseases caused by changes in protein trafficking and release.
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PMID:Role of PKC-dependent pathways in HNE-induced cell protein transport and secretion. 1289 98

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of colorectal carcinomas and represents a target for therapeutic interventions with signal transduction inhibitors. We investigated the ability of CI-1033 to induce apoptosis and inhibition of proliferation in the colorectal cancer cell lines DiFi and Caco-2, which both express high levels of EGFR. While in Caco-2 cells CI-1033 treatment at a concentration 0.1 microM for 72 hours demonstrated only antiproliferative (53.7 +/- 4.3%) but no pro-apoptotic effects, treatment of DiFi cells resulted in a reduced proliferation rate (31.4 +/- 3.1%) and in apoptosis (44.2 +/- 8.9%). In order to define proteins involved in the regulation of apoptosis, we aimed to determine differences in the proteome profile of both cell lines before and after treatment with CI-1033. Cellular proteins were analyzed by 2-D gel electrophoresis followed by computational image analysis and mass spectrometry. Our data show that DiFi cells differ from Caco-2 cells in nine significantly upregulated proteins, and their potential role in apoptosis is described. We demonstrate that induction of apoptosis was triggered via caspase-independent pathways. Overexpression of leukocyte elastase inhibitor (LEI) and translocation of cathepsin D to the cytosol accompanied by upregulation of other defined proteins resulted in Bax-independent AIF translocation from mitochondria into the nucleus and apoptosis. Definition of these proteins can pave the way for functional studies and contribute to a better understanding of the effects of CI-1033 and the pathways of caspase-independent cell death.
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PMID:Irreversible pan-ErbB tyrosine kinase inhibitor CI-1033 induces caspase-independent apoptosis in colorectal cancer DiFi cell line. 1615 50