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)

Muscle tissue levels of lysosomal catheptic enzymes, such as cathepsins D, A, B1, C, and dipeptidyl peptidase II, were measured in control subjects and patients with muscular dystrophies, polymyositis, and certain denervating diseases. The results show that, in general, the activities of these enzymes are increased in muscles of patients with muscular dystrophies and other diseases. The increases in cathepsin D and autolytic activities are not significant until the late stage of the disease process. Cathepsins A, B1, and C are, however, significantly elevated in mildly affected dystrophic and other diseased muscles. Of these catheptic enzymes, cathepsin B1 displays the highest rise at an early stage, suggesting that it may be one of the rate-controlling enzymes of proteolysis. Dipeptidyl peptidase II is increased slightly in dystrophic and other myopathic muscles but is unchanged in denervated muscle. These data clearly implicate the lysosomal group of proteinases as largely responsible for mediating muscle breakdown in the muscular dystrophies and certain other muscle and neuromuscular diseases in man.
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PMID:Muscle breakdown and lysosomal activation (biochemistry). 28 25

Considerable progress has been made in the localization of chemical substances within the gas-exchange zones of vertebrate lungs since cytochemical techniques suitable for use with the electron microscope have been developed. The light microscope, an instrument with an effective resolution limit of about 0.2 micron, is ill-suited for studying regions such as these where small tissue elements are arranged in a complex manner. A wide range of acid hydrolases have been detected in the vacuoles and dense bodies of alveolar macrophages by means of cytochemical techniques. The enzymes demonstrated in this way include acid phosphatase, aryl sulphatase, cathepsin D, beta-glucuronidase, acetyl glucosaminidase, nonspecific esterase, dipeptidyl peptidase II and dipeptidyl peptidase IV. Such enzymes are, of course, to be expected in the lysosomes of cells which have a primary phagocytic role. Nevertheless, it must be confessed that very little is yet known about the actual mechanism of phagocytosis or of the fate of the digested material. It is fortunate, however, that some of the tools which are likely to be of value in research on these aspects of macrophage function are currently being developed. Of particular interest in this connection are the immunocytochemical techniques which permit the localization of surface-associated antigens and intracellular contractile proteins. It must be emphasized that phagocytosis is not the only function of macrophages in the gas-exchange zone of the lung. These cells are thought to be involved in the presentation of exogenous antigenic material to the reactive cells of the lymphoid system. Recent research has also indicated that mammalian alveolar macrophages synthesize a diverse range of substances. Furthermore, the elastases associated with pulmonary macrophages are now thought to be involved in the pathogenesis of emphysema. All of the above-mentioned activities are of great biological and clinical significance and, consequently, merit the cytochemists' attention in future. The epithelial lining of the greater part of the pulmonary gas-exchange area is composed of type I pneumonocytes. In terms of ultrastructure, these are very specialized cells; their extensive and highly-attenuated cytoplasmic processes form the outer layer of the air-blood barrier. No special carrier systems have been identified within type I pneumonocytes and this is in keeping with the claims that oxygen is transferred across the alveolar tissue barrier by a process of simple diffusion. Type II pneumonocytes, in contrast, have considerable metabolic activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytochemistry of the gas-exchange area in vertebrate lungs. 355 66

Rabbit thyroids contain cathepsin D (CD) and several thiol endopeptidases including cathepsin B and three newly described enzymes (cathepsins 180K, 110K, and 45K). The present paper assesses the relative physiological importance of these enzymes in thyroglobulin degradation in rabbits. Thyroidal thiol endopeptidase [thiol thyroglobulin hydrolase (thiol TgH)] activity increased in the absence of changes in CD activity in animals treated with 10 U bovine TSH. Peak enzyme activity occurred 24 h after injection of hormone. After 20 U bovine TSH, thiol endopeptidase activity increased by approximately 100%, whereas CD increased by 50%. The increase in thiol enzyme activity was attributed both to cathepsin B and to the other thiol endopeptidases. The lysosomal acid hydrolases acid phosphatase and dipeptidyl peptidase II were unaffected by TSH at either dose level. Thiol TgH activity, but not CD activity, was decreased in thyroids of rabbits treated with T4 [5 micrograms/(100 g BW X day)] for 1 week. All thyroidal acid hydrolases examined were suppressed in animals receiving T4 for 3 weeks. Thiol TgH activity was localized primarily to a lysosome-enriched fraction of thyroid homogenates. Our results suggest that the thiol proteases probably are the most important endopeptidases in thyroglobulin hydrolysis in vivo and that their activities are influenced by TSH.
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PMID:Stimulation of thyroidal thiol endopeptidases by thyrotropin. 636 Jun 67

Using immunohistochemical or histochemical techniques lysosomal proteases have been localized in muscle cells. These include two exopeptidases (dipeptidyl peptidase I and II) and three endopeptidases (cathepsins B, D, and H). In general, the enzymes varied in apparent activities with the soleus muscle always more reactive than the extensor digitorum longus (EDL) of the rat. Cathepsin B and dipeptidyl peptidase I were localized primarily in subsarcolemmal regions whereas cathepsin H and dipeptidyl peptidase II were scattered throughout the sarcoplasm consistent with other observation of two populations of muscle lysosomes. However, cathepsin D could not be localized in either type of lysosome by similar histochemical techniques. Using immunohistochemical techniques, the protease inhibitors alpha 1-antitrypsin and alpha 1-inhibitor3 were recognized in intracellular compartments within muscle cells. alpha 1-antitrypsin appeared scattered throughout the cytoplasm while alpha 1-inhibitor3 was localized in discrete subsarcolemmal regions. Both inhibitor content and protease activity were diminished in skeletal muscles following streptozotocin-induced diabetes.
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PMID:Identification and possible regulation of muscle cell lysosomal protease activity by exogenous protease inhibitors. 704 96

Recent evidence, based upon immunocytochemical and histochemical analysis of brain cortical tissue from alzheimer's disease patients, has suggested that altered activity and/or distribution of the lysosomal proteases cathepsins B and D may be implicated in the abnormal protein processing pathway resulting in formation of the neurotoxic amyloid A4 peptide, characteristic of this neurodegenerative disorder. We have therefore compared, via biochemical assay techniques using conventional or specially synthesised (corresponding to protein cleavage points of relevant to A4 peptide formation) fluorogenic substrates, the levels of activity of the lysosomal proteases cathepsins B, D, H and L, and dipeptidyl aminopeptidases I and II in frontal cortex (grey/white matter) from control and Alzheimer's disease patients. For comparative purposes, activity levels of the above enzymes were also determined in frontal cortex tissue from cases with Lewy body dementia and Parkinson's disease, and in caudate tissue from control and Huntington's disease cases. There was no significant difference in activity for any protease types in tissue from control cases and cases with Alzheimer's disease, Lewy body dementia or Parkinson's disease, with the exception of reduced dipeptidyl aminopeptidase II activity in Lewy body dementia and Parkinson's cases. We have therefore been unable to confirm a potential role for lysosomal cathepsins in the characteristic neurodegeneration associated with Alzheimer's disease; however the finding of significant increases in activity of dipeptidyl aminopeptidase II, cathepsin H and cathepsin D specifically in cases with Huntington's disease is of particular note. We therefore suggest the potential role of the latter enzymes in the pathogenesis of Huntington's disease requires further investigation.
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PMID:Comparison of cathepsin protease activities in brain tissue from normal cases and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and Huntington's disease. 756 49

Lysosomal serine and cysteine proteases are reported to play a role in collagen degradation. In this study, the activities of the lysosomal cysteine proteases cathepsin B and H, dipeptidyl peptidase I, and the serine protease tripeptidyl peptidase I and dipeptidyl peptidase II, all ascribed a role in collagen digestion, were compared with those of the aspartate protease cathepsin D, and lysosomal glycosidases in leukocytes from rheumatoid arthritis patients at different stages of the disease. In all patients the activities of cysteine protease cathepsin B, dipeptidyl peptidase I, aspartate protease cathepsin D, and two glycosidases were elevated, but the activities of the serine proteases tripeptidyl peptidase I, dipeptidyl peptidase II, and the cysteine protease cathepsin H was unchanged. The magnitude of the increased activity was correlated with the duration of the disease. Patients with long-standing RA (10 years or more) had higher cysteine protease activity in their leukocytes than did those with disease of shorter duration. This tendency suggests that elevated lysosomal cysteine protease activities, together with aspartate protease cathepsin D and lysosomal glycosidases (but not serine proteases), are associated with progression of rheumatoid arthritis.
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PMID:Lysosomal peptidases and glycosidases in rheumatoid arthritis. 1210 54