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)

The mechanisms of hydrocortisone and adrenalin action on the structure and function of the lysosomal-vacuolar cell apparatus were studied in experiments on liver sections of Wistar rats. The sections were incubated in Krebs-Ringer bicarbonate buffer, pH 7.4 (95% O2 and 5% CO2) at 37 degrees C for 2 h. Hydrocortisone (10(-5) M) and adrenalin (10(-4) M), added to an incubation medium, were shown to produce a labilizing effect on lysosomal membranes, increasing free activity of acid phosphatase and cathepsin D and osmotic sensitivity of lysosomes. alpha-adrenergic blocker dihydroergotamine (3.4 x 10(-5) M) blocked an increase in free activity of acid phosphatase as a result of adrenalin action but did not eliminate hydrocortisone labilizing action. beta-adrenergic blocker propranolol (3 x 10(-4) M) lowered free activity indices and osmotic sensitivity of lysosomes to control values both in the presence of adrenalin and hydrocortisone. The labilization of lysosomal membranes in liver sections was also observed after adding dibutyril-cAMP (10(-8) M) or monobutyril-cGMP (10(-13)-10(-9) M) into the incubation medium.
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PMID:[The mechanism of action of hydrocortisone and adrenaline on the hepatic lysosomal apparatus]. 233 Mar 63

Plasmodium requires a living cell for growth and reproduction. Intraerythrocytically the parasite stores no reserve carbohydrate, relying entirely on host-supplied glucose and certain amino acids (glutamic acid) for its energy. Plasmodia are microaerophiles degrading glucose primarily to lactate rather than to CO2. The limited amounts of oxygen utilized may serve for biosynthetic purposes (e.g. pyrimidine biosynthesis) rather than being involved in an energy-yielding electron transport chain. Evidence for a parasite pentose pathway is weak since glucose-6-phosphate dehydrogenase has rarely been found; paradoxically, activity for 6-phosphogluconate dehydrogenase, the next enzyme in the pathway, is consistently identified. The parasites synthesize pyrimidines de novo, but being incapable of de novo purine biosynthesis they require preformed purines. Exogenously supplied purine, notably hypoxanthine derived from catabolism of erythrocytic ATP, is taken up and incorporated whereas pyrimidines are not. The capacity for de novo amino acid biosynthesis is limited and presumably haemoglobin supplies most of the amino acids required by the parasite. Degradation of haemoglobin, involving parasite proteases, notably a cathepsin D-like enzyme, leaves a characteristic golden-brown residue, haemozoin. Haemozoin consists of dimers of ferriprotoporphyrin IX, methaemoglobin and plasmodial proteins. For some species, isoleucine and methionine must be supplied exogenously for good plasmodial growth. Infected erythrocytes characteristically show altered permeability properties, changes which in large part contribute to parasite growth while at the same time impairing red cell function.
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PMID:Metabolism and surface transport of parasitized erythrocytes in malaria. 655 Dec 36

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

The polyamines putrescine, spermidine, and spermine and ornithine decarboxylase (ODC), the rate-limiting enzyme in their biosynthetic pathway, play an important role in cell proliferation, differentiation, and transformation. In the present study, we have analyzed polyamine concentrations and ODC activity in samples from benign breast diseases (n = 36), benign breast tissue adjacent to the primary carcinoma (n = 19), and breast carcinoma (n = 104). ODC activity in primary carcinoma was significantly higher (2.42 +/- 0.22 nmol CO2/h g; P < 0.001) than that found in benign breast (0.62 +/- 0.15 nmol CO2/h g) or in breast tissue adjacent to the primary carcinoma (0.52 +/- 0.16 nmol CO2/h g). The total polyamine content of breast cancer tissues was higher than in benign breast diseases (704.3 +/- 38.3 nmol/g wet weight versus 295.8 +/- 27.4 nmol/g wet weight) and correlated well with ODC activity (Pearson, r = 0.42; P < 0.001). ODC activity correlated with histological grade, peritumoral lymphatic or blood vessel invasion, S-phase fraction, and cathepsin D. Total polyamine concentration increased with S-phase fraction, cathepsin D, and aneuploidy. No significant correlation was found between ODC or polyamines and tumor size, lymph node involvement, or steroid receptor status. A major finding in our study was that ODC activity was an independent prognostic factor for recurrence and death. The results indicate that the estimation of ODC activity and polyamines in human breast carcinoma might be useful to determine tumor aggressiveness and suggest that ODC may have a potential value as both a prognostic factor and a chemoprevention target in human breast cancer.
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PMID:Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: correlation with clinicopathologic parameters. 1047 83