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)

The distribution of tryptase in various human tissue high-salt extracts (skin, lung, pancreas, liver, kidney, and spleen) was studied. Tryptase activity was compared with tissue histamine concentration, chymase activity, and cathepsin D, and histamine-N-methyltransferase (HMT) activities. Tryptase activity, found biochemically in tissue extracts, was localized in tissue sections by an enzyme-histochemical method using peptide 4-methoxy-2-naphthylamide substrates and Fast Garnet GBC as the chromogen. The highest levels of tryptase activity were found in lung and skin extracts. Liver, kidney, and spleen extracts displayed only a little activity. The distribution of histamine was similar to that of tryptase, whereas distributions of cathepsin D and HMT were quite different from that of tryptase. High-salt extracts of lung contained no detectable chymase activity, but in skin extracts this activity was high. Using an enzyme-histochemical method, the tryptase activity in tissue sections seemed solely to be confined to cells, which were granular and Giemsa positive after the red azo dye had been removed with Tween 20. Skin and lung sections contained the highest number of positively stained cells. The inhibition properties of tryptase, found in both tissue extracts and sections, and the substrate profile in tissue sections were identical. Human leukocyte preparation was negative for tryptase when stained enzyme-histochemically. The present results suggest that tryptase in human tissues is found only in the mast cells. The enzyme seems to be identical in the various human tissues studied because the different high-salt extracts were immunologically cross-reactive when tested with a rabbit polyclonal antibody against skin tryptase.
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PMID:Biochemical and histochemical evaluation of tryptase in various human tissues. 267 65

We here ascertain whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (CD, a lysosomal hydrolase that seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori (Hp) infection. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer, and 11 with duodenitis. Tryptase and CD were measured in mucosal biopsies (body and antrum of the stomach and duodenum) using IRMA methods. Hp infection was histologically evaluated (Giemsa). Tryptase and CD levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. In Hp-positive patients the CD mucosal content was higher while tryptase mucosal levels were lower than in Hp-negative patients. Tryptase was correlated with gastrin content. CD seems to be mainly related to the phlogistic reaction of the mucosa to Hp infection; tryptase may reflect an indirect link between Hp infection, gastrin release, and the function of mast cells.
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PMID:Influence of Helicobacter pylori on tryptase and cathepsin D in peptic ulcer. 758 35

The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others, Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method. Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated with Helicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa to Helicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells.
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PMID:Are tryptase and cathepsin D related to Helicobacter pylori infection and mucosal gastrin in peptic ulcer? 820 35

Dendritic cells (DC) are known to present exogenous protein Ag effectively to T cells. In this study we sought to identify the proteases that DC employ during antigen processing. The murine epidermal-derived DC line Xs52, when pulsed with PPD, optimally activated the PPD-reactive Th1 clone LNC.2F1 as well as the Th2 clone LNC.4k1, and this activation was completely blocked by chloroquine pretreatment. These results validate the capacity of XS52 DC to digest PPD into immunogenic peptides inducing antigen specific T cell immune responses. XS52 DC, as well as splenic DC and DCs derived from bone marrow degraded standard substrates for cathepsins B, C, D/E, H, J, and L, tryptase, and chymases, indicating that DC express a variety of protease activities. Treatment of XS52 DC with pepstatin A, an inhibitor of aspartic acid proteases, completely abrogated their capacity to present native PPD, but not trypsin-digested PPD fragments to Th1 and Th2 cell clones. Pepstatin A also inhibited cathepsin D/E activity selectively among the XS52 DC-associated protease activities. On the other hand, inhibitors of serine proteases (dichloroisocoumarin, DCI) or of cystein proteases (E-64) did not impair XS52 DC presentation of PPD, nor did they inhibit cathepsin D/E activity. Finally, all tested DC populations (XS52 DC, splenic DC, and bone marrow-derived DC) constitutively expressed cathepsin D mRNA. These results suggest that DC primarily employ cathepsin D (and perhaps E) to digest PPD into antigenic peptides.
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PMID:Identification of proteases employed by dendritic cells in the processing of protein purified derivative (PPD). 1528 85

The first reported human anaphylactic death is considered to be the Pharaoh Menes death, caused by a wasp sting. Currently, anaphylactic cardiovascular events represent one of most frequent medical emergencies. Rapid diagnosis, prompt and appropriate treatment can be life saving. The main concept beyond anaphylaxis lies to myocardial damage and ventricular dysfunction, thus resulting in cardiovascular collapse. Cardiac output depression due to coronary hypoperfusion from systemic vasodilation, leakage of plasma and volume loss due to increased vascular permeability, as well as reduced venous return, are regarded as the main causes of cardiovascular collapse. Clinical reports and experiments indicate that the human heart, in general, and the coronary arteries, in particular, could be the primary target of the released anaphylactic mediators. Coronary vasoconstriction and thrombosis induced by the released mediators namely histamine, chymase, tryptase, cathepsin D, leukotrienes, thromboxane and platelet activating factor (PAF) can result to further myocardial damage and anaphylaxis associated acute coronary syndrome, the so-called Kounis syndrome. Kounis syndrome with increase of cardiac troponin and other cardiac biomarkers, can progress to heart failure and cardiovascular collapse. In experimental anaphylaxis, cardiac reactions caused by the intracardiac histamine and release of other anaphylactic mediators are followed by secondary cardiovascular reactions, such as cardiac arrhythmias, atrioventricular block, acute myocardial ischemia, decrease in coronary blood flow and cardiac output, cerebral blood flow, left ventricular developed pressure (LVdp/dtmax) as well as increase in portal venous and coronary vascular resistance denoting vascular spasm. Clinically, some patients with anaphylactic myocardial infarction respond satisfactorily to appropriate interventional and medical therapy, while anti-allergic treatment with antihistamines, corticosteroids and fluid replacement might be ineffective. Therefore, differentiating the decrease of cardiac output due to myocardial tissue hypoperfusion from systemic vasodilation and leakage of plasma, from myocardial tissue due to coronary vasoconstriction and thrombosis might be challenging during anaphylactic cardiac collapse. Combined antiallergic, anti-ischemic and antithrombotic treatment seems currently beneficial. Simultaneous measurements of peripheral arterial resistance and coronary blood flow with newer diagnostic techniques including cardiac magnetic resonance imaging (MRI) and myocardial scintigraphy may help elucidating the pathophysiology of anaphylactic cardiovascular collapse, thus rendering treatment more rapid and effective.
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PMID:Anaphylactic cardiovascular collapse and Kounis syndrome: systemic vasodilation or coronary vasoconstriction? 3030 71