Search PubMed⌕ Search

Biomedical subjects

K Worowski

Publications and source records attributed to K Worowski.

At least 19 recordsLinked to original sources
PubMed2000

Separation of cathepsin A-like enzyme and the proteasome: evidence that lactacystin/beta-lactone is not a specific inhibitor of the proteasome.

Previous studies have described a human platelet cathepsin A-like enzyme with a number of similarities to the "acidic" and "neutral" chymotrypsin-like activities of the proteasome. This includes its strong inhibition by the highly specific proteasome inhibitor Lactacystin/beta-lactone, suggesting that either the Cbz-Phe-Ala-hydrolyzing activity attributed to cathepsin A was due to the chymotrypsin-like activity of the proteasome or that lactacystin was not a specific inhibitor of the proteasome. In the present study we discard the first possibility on the basis of the following findings: (a) human platelet cathepsin A, unlike proteasome, binds to concanavalin A, and does not bind to Heparin-Sepharose at pH 7.4; (b) neither the chymotrypsin-like activity of the proteasome, nor proteasome antigens are detected in the cathepsin A preparation; (c) purified proteasome does not exhibit Cbz-Phe-Ala-hydrolyzing activity; (d) Z-lle-Glu-(Ot-Bu)Ala-leucinal (PSI), a compound that selectively inhibits the chymotrypsin-like activity of the proteasome at a concentration of 10 microM has no inhibitory effect on the carboxypeptidase activity of cathepsin A; (e) cathepsin A, free of the proteasome, is completely inhibited by micromolar concentrations of lactacystin/beta-lactone. It is therefore concluded that lactacystin/beta-lactone is not a specific inhibitor of the proteasome.

Acetylcysteine↗
PubMed1998

Inhibitors of pepsin, trypsin and chymotrypsin in seeds of plants consumed by humans and animals. I. Evaluation of pepsin, trypsin, and chymotrypsin inhibitors activity in seeds of 26 plant species.

Antipepsin, antitrypsin and antichymotrypsin activity was determined in seed extracts of 26 plants consumed by humans and animals (small bean, broad bean, pumpkin, kidney bean, charlock, pea, buckwheat, barley, maize, flax, lupine, poppy, almond, peanut, hazel, walnut, oat, millet, wheat, rice, rape, sunflower, lentils soya bean, vetch, rye). Antipepsin activity is found in the seeds of small bean, pumpkin, flax, peanut, walnut, oat, wheat, sunflower, lentils and soya bean. Antitrypsin and antichymotrypsin activities are of different intensity in seed extracts of all examined plants.

Animals↗
PubMed1997

Lactacystin, a specific inhibitor of the proteasome, inhibits human platelet lysosomal cathepsin A-like enzyme.

Lactacystin, the most specific inhibitor of the proteasome, strongly inhibited at pH 5.5 the activity of human platelet lysosomal cathepsin A-like enzyme. At a concentration as low as 1-5 microM it almost completely decreased the hydrolysis rate of cathepsin A specific substrates: Cbz-Phe-Ala and FA-Phe-Phe. This inhibition was probably due to the lactacystin intermediate beta-lactone formed during 10 min hydrolysis at pH 8.0 since nonhydrolyzed inhibitor did not affect cathepsin A activity. Basing on similarities in the inhibitor sensitivity, pH optimum, and substrate preferences it is suggested that the cathepsin A-like activity may be involved in chymotrypsin-like activity of the proteasome.

Acetylcysteine↗
PubMed1997

Tripeptide methylketones: synthesis and antiplasmin activity.

A series of tripeptide methylketones with C-terminal lysine was obtained via Dakin-West method and tested for their antiplasmin activity with the use of antifibrinolytic and antiamidolytic tests. The tripeptide methylketones has been found to inhibit plasmin, however with much lower potency than respective aldehydes.

Chemical Phenomena↗
PubMed1997

Proteolytic enzymes in proliferation and neoplastic metastases formation.

Metalloproteases, plasminogen urokinase activator, plasmin and cathepsins enable the expansion of neoplastic tumors, leading to metastases formation. They cause neoplastic cells to detach from tumor, facilitate cell movement, implantation and participate in tumor vascularization. The regulation of these processes is accomplished during the synthesis and activation of proenzymes. Enzyme activity control is realized by their bonds with cellular membranes, and inhibitor action.

Animals↗
PubMed1997

Plasminogen activators and plasmin in lung cancer.

Urokinase plasminogen activator and plasmin contribute to detach neoplastic cells from solid tumor and facilitate the movement of these cells through interstitium and capillary walls as well as infiltration of the surrounding structures. Plasminogen activators inhibitors fulfill a regulatory function in these processes. Determining activity and concentration, finding subcellular, cellular and zonal localization of every component of plasminogen activation system has diagnostic and prognostic importance in different lung cancer types.

Fibrinolysin↗
PubMed1997

Prolidase activity and beta 1 integrin expression in moderately and poorly differentiated lung adenocarcinomas.

Primary human lung adenocarcinomas were divided into two groups according to the degree of histologic differentiation: G2-moderately and G3-poorly differentiated tumors. Each group was compared with normal lung tissue in respect to prolidase activity, its ability to interact with specific antibody, free proline and beta 1 integrin subunit content as well as ability of beta 1 integrin subunit to interact with specific antibody. It was found that prolidase activity in lung adenocarcinomas G3, was significantly elevated in comparison to normal lung tissue. In lung adenocarcinoma G2 no significant changes in the enzyme activity were observed. Increase in the enzyme activity was accompanied by increase of free proline content in the tissues. The western blot analysis revealed that prolidase of lung adenocarcinomas is identical to prolidase originated in control lung tissue. It was noticed that elevated activity of prolidase in adenocarcinomas G3 was accompanied by its high expression. In respect to beta 1 integrin expression, known to play an important role in metastasis, no difference was found between adenocarcinoma groups and the control lung tissue. The presented data suggest that the level of prolidase activity in lung adenocarcinoma may serve as a more sensitive marker for the histologic degree of malignancy, than the level of beta 1 integrin expression.

Adenocarcinoma↗
PubMed1997

Activity of liver proteases in experimental methanol intoxication.

Intoxication of rats with methanol (1.5 and 3.0 g/kg body weight) led to a significant, time- and dose-dependent decrease in the activities of cathepsins A, B and C, while the activity of cathepsin D was unaffected. The decrease was associated with a different partial release of individual cathepsins to the post-lysosomal fraction.

Animals↗
PubMed1996

Influence of dipeptide derivatives of S-substituted cysteines on the time of fibrinolysis.

Amino acids containing sulphur, dipeptide derivatives of methionine and S-substituted derivatives of cysteine are potent antifibrinolytic agents. The structural moiety of the substances responsible for the effect on the clot formation is not known. Present study was undertaken in order to evaluate the effect of some analogues of dipeptides containing S-substituted derivatives of cysteine with the formula A-Cys(S-X)-Y (where A-amino acid, X-benzyl, butyl, hexyl, nonyl and Y-OH or OMe) on clot dissolution under the antifibrinolytic test conditions. It has been found that dipeptide derivatives of S-substituted cysteine (except benzyl derivative) at low concentration evoke antifibrynolytic activity, while at high concentration they prevent clot formation. The results suggest that antifibrinolytic activity of tested compounds at low concentration may be due to the formation of antifibrinolitycally active conformation, while high concentration overcome the effect.

Antifibrinolytic Agents↗
PubMed1995

Comparison of morphological and biochemical changes of BAL-isolated cells in experimental lung emphysema.

The aim of the study was to evaluate the protease and antiprotease activity in the fluid obtained from the culture of cells isolated from the lungs of animals with experimental emphysema. An attempt was made to correlate the results of biochemical examinations with adherence degree and ultrastructural changes of the surface of BAL-isolated cells. The experiment was carried out on male Wistar rats, of 180-220 g b.w. Two i.p. injections of BCG-vaccine (4 x 10(8) microorganisms) on the 1st and 14th day were applied as macrophage mobilizing and activating agent. Papain (2 mg/l ml/100 g b.w.) was given once i.t. on the 21st day. The animals were sacrificed on the 28th day of the experiment. We found a correlation between the increase in the cell adherence and ultrastructural changes (in SEM), suggesting an increased activity of the cells isolated from BCG-treated rats. In the culture medium of cells isolated from the rats which were given BCG or papain and BCG+papain we observed an increased base protease activity and decreased Cathepsin D activity comparing with the control group. Increased antitrypsin activity in the BCG and BCG+papain-treated rats and decreased antitrypsin activity in papain-treated rats only was observed, too. There was no obvious difference in the levels of the antiplasmin and antichymotrypsin activities between the groups. The present results indicate that activated pulmonary macrophages are one of the sources of the protease-antiprotease intraalveolar imbalance. However, an increased production of proteolytic enzymes may not be the only factor responsible for the progression of lung emphysema in BCG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cathepsin D activity in the intestinal wall in experimental untreated hemorrhagic shock.

The total cathepsin D activities in the intestinal wall and in venous mesenteric and arterial systemic blood were investigated on the rats in untreated hemorrhagic shock lasting 60 minutes. We observed a decrease in cathepsin D activity in homogenates of respective segments of small and large bowels and an increase in the enzyme activity in blood serum of both origin. The shock resulted in lowering protein concentration in the intestinal wall and its increase in the mesenteric blood. We found a negative correlation between cathepsin D activity in the intestinal wall and its morphological destruction. Molecules of the enzyme, after liberation from lysosomes due to hemorrhagic shock, are translocated to the circulation and probably to the gut lumen. Liberation of the intestinal cathepsin D may contribute to the local damage and multiorgan failure in hemorrhagic shock.

Amino Acids↗
PubMed1995

Disturbances of hemostasis during declamping shock.

The aorta, above or below renal arteries was clamped for 60 minutes, in a canine model. The blood was taken for testing from above the aorta bifurcation before clamping, after 30 minutes of its duration, directly after declamping and every 30 minute during next 4 hours. Irrespective of clamping level, the platelet count, clot retraction and prothrombin consumption do not undergo significant changes. However, the activity of platelet factor 4 is increased. Prothrombin time, recalcination time, kaolin-kephalin time and the activities of factors V, VII, XI and XII do not differ as well. Thrombin time is prolonged and antithrombin III activity is reduced. Euglobulin fibrinolysis time undergoes prolongation and antiplasmin content is increased. The observed changes show a variable tendency, regardless of clamping level and increase with the passage of experiment time. An increase in the coagulation activity and a decrease in the fibrinolytic activity of the blood plasma may be a resultant of the changes. Finally it may promote thrombus formation and indicates the preventive use of heparin.

Animals↗
PubMed1995

Hemostatic activity of organs in declamping shock.

The aim of the study was to determine the haemostatic components activity of organs in declamping shock. The abdominal aorta was cross-clamped below or above renal arteries. No significant changes in tromboplastic and antithrombin activities were found in the kidney, liver, lung, heart and skeletal muscle. Renal cortex and medulla as well as the lungs show higher plasminogen activator activity and considerably higher antiplasmin activity. Diminished fibrinolysis in the kidney and the lung may promote thrombotic complications.

Animals↗
PubMed1995

Activity of membrane, cytosol and lysosome enzymes in organs and blood serum during declamping shock.

The aim of the study was to evaluate the enzyme activity of cellular membranes (GGT), cytosol (ALT, AST) and lysosome (AP, AcP) in the cytosol, whole homogenate and blood serum during declamping shock, following release of abdominal aorta cross-clamping. The aorta was clamped for 60 minutes. An increase in GGT, AP and AcP activities in the cytosol and whole homogenate of the renal cortex, renal medulla, liver, lung, heart and the skeletal muscle occurs after declamping. Rise in the enzymatic activity, especially of acid phosphatase is higher when the aorta above renal arteries was clamped. However, its activity in the blood serum remains unchanged. Alterations in the distribution and the activity of the studied enzymes may indicate that aortic clamping damages the endoplasmic reticulum and lysosomal membranes. Yet, cellular membranes preserve their structural and functional integrity.

Acid Phosphatase↗
PubMed1995

Cathepsin D activity and protein degradation products in organs and blood during experimental declamping shock.

Aortic cross-clamping in dogs for 60 min causes an increase in cathepsin D activity in the kidney, liver, lung, heart, skeletal muscle and the blood serum. It causes no changes in the content of protein and its degradation products of the examined organs, apart from the lungs, where the above parameters are higher. The intensity of the observed changes in the kidney and other organs does not depend on the level of aortic cross-clamping (above or below renal arteries).

Animals↗