Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysosomal membrane instability and platelet activation are both associated with acute myocardial ischemia. The effect of ibuprofen on cathepsin D as a marker of lysosomal membrane "leakiness" and thromboxane B2 as a marker of platelet activation was evaluated in 44 patients with angina pectoris. Samples of blood analyzed for cathepsin D, thromboxane B2, and lactate were withdrawn from the coronary sinus and brachial artery before and after pacing to 140 beats/min for 4 minutes. Myocardial ischemia was assessed by determination of transmyocardial lactate extraction or production. Ibuprofen (800 mg) or placebo was administered orally 2 hours before cardiac catheterization. Patients were classified into 4 groups on the basis of administration of placebo or ibuprofen and the presence or absence of myocardial ischemia as determined by demonstration of lactate extraction or production after atrial pacing. In patients with lactate extraction, no significant efflux of cathepsin D or thromboxane B2 occurred after pacing. In patients with lactate production given placebo, a 64 +/- 25% increase in the thromboxane B2 level and a 113 +/- 37% increase in cathepsin D activities occurred in the coronary sinus effluent sampled after pacing. In contrast, in patients with comparable coronary artery disease and comparable lactate production who were given ibuprofen, no release of thromboxane B2 (p = 0.05 compared with patients given placebo) or cathepsin D (p less than 0.01 compared with patients given placebo) occurred after pacing-induced ischemia. These findings suggest that ibuprofen stabilizes membranes and prevents platelet-activated release of thromboxane A2 in pacing-induced myocardial ischemia.
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PMID:Beneficial effects of ibuprofen in pacing-induced myocardial ischemia. 682 34

Alterations in myocardial acid hydrolases in acute ischemia were studied in relation to the evolution of cardiac cellular necrosis by the determination of cathepsin D, acid phosphatase (AcPase), and beta-glucuronidase activities of the myocardial fractions and by electron microscopic cytochemical studies on AcPase in the canine heart. In the normal myocardium, the same level of activity of acid hydrolases was found in sarcoplasmic reticulum (SR) as in the lysosome fraction. In electron microscopy, AcPase reaction products were observed markedly in SR and moderately in lysosomes, in residual bodies, and in Golgi apparatus. In the ischemic myocardium, at 20 to 30 min after coronary ligation, activation of these enzymes was observed in both SR and lysosomes, and at 60 to 90 min they were decreased in the particles and, in turn, increased in the cytoplasm accompanying the ischemic fine structural changes. At 2 to 3 hr those acid hydrolase activities in the cytosol were decreased, indicating the loss of enzymes from necrotic myocardial cells. Acid hydrolases are the most important factor for the evolution of ischemic myocardial necrosis by being activated not only in lysosomes but also in SR and by being released to the cytoplasm to disintegrate the cellular structures.
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PMID:Acid hydrolases in the initiation of ischemic myocardial necrosis. 685 64

The calcium channel blocking agent, nifedipine, was studied during global ischemia and reperfusion in isolated cat hearts perfused with Krebs-Henseleit solution. Nifedipine was added to the reservoir and 0.1 micrograms/ml perfusate/hr of nifedipine was infused for 150 min. After 120 min of ischemia (flow at 1% of control), the heart was reperfused with nifedipine-containing perfusate for 20 min and with nifedipine-free perfusate for an additional 25 min. In control hearts, nifedipine significantly reduced the percent free activity of the lysosomal protease cathepsin D (P less than 0.01). In ischemic hearts, nifedipine protected against the increased myocardial tissue edema (P less than 0.01), the increased percent free cathepsin D activity (P less than 0.02) and the postreperfusion increased creatine kinase activity (P less than 0.01). Thus, nifedipine showed membrane stabilizing and cytoprotective activities in myocardial cells, after postischemic reperfusion. These data suggest that calcium ions contribute to the lysosome labilization and cytoplasmic enzyme leakage observed in ischemia and reperfusion, and that calcium channel blockade may protect myocardial cellular integrity during both ischemia and reperfusion.
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PMID:The protective effects of nifedipine in the isolated cat heart. 686 91

Isolated cat hearts were perfused with blood-free Krebs-Henseleit solution for 165 min. Ischemia was induced by reducing perfusion to 0.02 ml/min/g wet heart weight for 2 h followed by reperfusion at controls flows for 30 min. Hearts perfused with the thromboxane synthetase inhibitor OKY-1581 at concentrations of 5 X 10(-6) M were spared from the increases in circulating thromboxane B2 occurring in untreated ischemic hearts. After reperfusion, cardiac contractile force increased to a higher level in OKY-1581 treated hearts. This was associated with a lower coronary vascular resistance than in untreated ischemic hearts. OKY-1581 treated ischemic hearts exhibited lower perfusate and higher myocardial creatine kinase (CK) activity than untreated ischemic hearts, indicative of preservation of cellular integrity. Also, OKY-1581 treated ischemic hearts showed improved lysosomal stability as evidenced by a lower tissue percent free cathepsin D activity than untreated ischemic hearts. These results are consistent with a significant role of thromboxanes in the propagation of myocardial cellular damage during ischemia.
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PMID:Salutary actions of thromboxane synthetase inhibition during global myocardial ischemia. 689 41

Intracellular cathepsin D is thought to play a role in myocardial injury produced by ischemia and hypoxia. Pepstatin, a known inhibitor of cathepsin D, was infused into isolated guniea pig hearts (Langendorff preparation) in order to observe if such an administration of pepstatin would protect against the effects of a two minute exposure to hypoxia. Hypoxia was produced by exposing the hearts to perfusion fluid aerated with 20% 02/5% CO2/75% N2 and containing 0.5 microgram/ml of norepinephrine. Contractile force, heart rate, coronary flow and ECG were monitored. Samples of heart tissue were assayed for cathepsin D activity. Infusion of 0.06 mg/min of pepstatin for 30 minutes produced no significant alterations in the parameters of cardiac function studied. However, this amount of pepstatin inhibited 97% of the cathepsin D activity of the hearts. The characteristics ECG alterations produced by hypoxia were significantly reduced after infusion of pepstatin. These data indicate that pepstatin may protect the heart against hypoxia-induced injury.
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PMID:Effects of pepstatin on reducing hypoxia-induced injury in the isolated guniea pig heart. 713 30

Activities and subcellular distributions of acid hydrolases, cathepsin D, acid phosphatase and beta-glucuronidase in myocardial subfractions were determined serially with reference to the initiation of myocardial necrosis in dog hearts with acute ischemia. The following results were obtained: 1) In the normal myocardium, respectable activities of three enzymes were obtained either in the sarcoplasmic reticulum or in the lysosome-containing fraction. 2) Thirty min after coronary ligation, an increase in the activities was observed in both lysosome and sarcoplasmic reticulum fractions of the ischemic heart muscle. After 60 to 90 min these activities were decreased rapidly in both fractions to about 70% of those of the normal myocardium with an increase in the cytosolic activity. Two to 3 hours after ligation, the reduction in the cytosolic activity was noted, indicating an escape of the enzymes from the necrotic myocardium. The subcellular distribution of these enzymes was further altered in the ischemic heart muscle for 12 to 14 hours reflecting an infiltration of the interstitial cells. These findings suggest that activation and release of acid hydrolases not only in lysosomes but also in the sarcoplasmic reticulum are one of the primary and the earliest factors for the evolution of ischemic myocardial injury which leads to necrosis.
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PMID:Studies on intracardiac acid hydrolases in the ischemic myocardial necrosis. 714 2

Prolonged starvation produces dramatic changes both in the lysosomal properties of the heart and in its energy stores and, therefore, might be expected to alter some of the characteristic cardiac responses to ischemia. To test this possibility we ligated the circumflex coronary artery of rabbits that had been fed normally or starved for 6 days. Ultrastructural evidence of myocytic damage following 30 to 120 minutes of ischemia was much less severe in the starved animals than in the normally fed group. The development of signs of irreversible injury (e.g., osmiophilic densities in mitochondria) was delayed for 1 hour or more by starvation. A similar delay occurred in the biochemical redistribution of cathepsin D activity and in the cytoplasmic release of acid hydrolases from lysosomes and sarcoplasmic reticulum. These results indicate a marked protective effect of starvation against myocardial ischemia. In addition, both in starved and in fed animals, ischemically induced release of lysosomal enzymes was closely linked temporally to the development of subcellular damage.
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PMID:Resistance to ischemic damage in hearts of starved rabbits: Correlation with lysosomal alterations and delayed release of cathepsin D. 740 33

Inactivation of Na+/K(+)-ATPase by partially reduced oxygen metabolites has been implicated in ischemia-reperfusion injury to heart and other organs. Because oxidation of many proteins makes them more susceptible to degradation by intracellular proteinases, we studied the effects of several such proteinases on native and H2O2-oxidized preparations of Na+/K(+)-ATPase from canine kidney (containing alpha 1 isoform of the catalytic subunit) and rat axolemma (containing alpha 2 and alpha 3 isoforms). Lysosomal cathepsin D degraded the native and the oxidized preparations at acid pH, but it was significantly more effective against the oxidized forms. m-Calpain had little or no effect on the native Na+/K(+)-ATPase preparations, but it digested the oxidized alpha-subunits of the axolemma and the kidney enzymes. mu-Calpain's effects were similar to those of m-calpain. Multi-catalytic proteinase which is known to degrade a large number of oxidized proteins, did not affect the native or the oxidized forms of Na+/K(+)-ATPase. The findings suggest that (a) during oxidative stress there may be accelerated degradation of the oxidatively damaged Na+/K(+)-ATPase, either through internalization and transport to lysosomes, or by the action of calpains at the membrane; and (b) those isoforms of the enzyme that are more sensitive to oxidants are more susceptible to degradation by the above processes.
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PMID:Different sensitivities of native and oxidized forms of Na+/K(+)-ATPase to intracellular proteinases. 820 42

The accumulation and localization of cathepsins E and D in the rat hippocampus and neostriatum during the neurodegenerating process induced by transient forebrain ischemia were investigated by immunoprecipitation and by immunohistochemistry using discriminative antibodies specific for each enzyme. While significant amounts of cathepsin D were found in both the hippocampus and the neostriatum of normal rats, cathepsin E was barely detectable in these tissues. No significant change in their levels was found in these tissues of postischemic rats for up to 3 days after transient forebrain ischemia. After 7 days of the treatment, cathepsin E was markedly increased in both tissues. Although the cathepsin D content in these tissues was also increased at this stage, the rate of increase was much less than that of cathepsin E. At the light microscopic level, the increased immunoreactivity for each enzyme was mainly found in reactive glial cells and degenerating neurons in the hippocampal CA1 subfield at 7 days postischemia. In the neostriatal dorsolateral portion, cathepsin D immunoreactivity was also increased in both reactive glial cells and degenerating neurons, whereas increased immunoreactivity of cathepsin E was only identified in reactive glial cells at 7 days postischemia. It was also found by double-immunostaining technique that the cathepsin E-positive glial cells were largely reactive microglial cells, whereas the cathepsin D-positive glial cells were associated mainly with reactive astrocytes. These results suggest that the accumulation of both cathepsins E and D in the regions of selective neuronal vulnerability may be associated with the postischemic development of intense gliosis and also probably neurodegenerative responses.
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PMID:Transient forebrain ischemia induces increased expression and specific localization of cathepsins E and D in rat hippocampus and neostriatum. 833 72

A pig model of liver ischemia and intestinal congestion was made by portal triad clamping (PTC) for 45 minutes to investigate the influence of PTC on intestine. The results were as follows: 1. The level of cathepsin D was increased significantly after PTC as compared with the value before clamping (P < 0.05); 2. The endotoxin and lactic acid were significantly increased after PTC comparing with those of pre-clamping (P < 0.05, P < 0.01) and the control group (P < 0.05, P < 0.01); 3. The intestinal mucosa had a significant damage (P < 0.05) after PTC. The results indicate that PTC can result in intestinal mucosal lesion and enterotoxin absorption. Therefore, the protection of intestinal functions is important in hepatic surgery and preoperative bowel preparation should be done.
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PMID:[Influence of portal triad clamping on the intestine in pigs]. 1068 49


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