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 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.
 ...
PMID:[The mechanism of action of hydrocortisone and adrenaline on the hepatic lysosomal apparatus]. 233 Mar 63

The acid phosphatase and cathepsin D activities and cAMP and cGMP levels in isolated perfused rat heart were investigated during various periods of ischaemic myocardial injury and postischaemic reperfusion. The effect of phosphodiesterase inhibitor--caffeine was also studied. Free acid hydrolases activities and cyclic nucleotide content were increased under 40 and 60 min ischemia and 20 min postischaemic reperfusion. Addition of 50 microM caffeine to perfusion solution after 30 min of ischaemia resulted in increase of cAMP level, cAMP/cGMP ratio, lysosomal bound activities of acid hydrolase and decrease of free acid hydrolase activities. The obtained results suggested that defect in cAMP synthesis might be present in lysosomal membranes labilization in cardiomyocytes injured during ischaemic conditions. Addition of such agents, as caffeine, which increased heart cAMP level, may be effective in lysosomal membranes stabilization under reversible heart ischaemia and reperfusion.
 ...
PMID:[Acid hydrolase activity and cyclic nucleotide contents in the rat heart during myocardial ischemia and postischemic reperfusion]. 255 45

Levels of cyclic nucleotides (CN) in cardiac, cerebral, and hepatic tissues were measured in the early postresuscitation period in rats exposed to systemic circulation arrest induced by clamping of the cardiac vascular bundle. Changes of CN levels in the examined tissues were different in principle. In the heart cAMP levels progressively reduced 30 and 60 min after resuscitation, whereas cGMP levels were increasing. On the contrary, in the liver cAMP levels increased and cGMP content reliably reduced. Levels of cAMP and cGMP reliably reduced in the basis cerebri, with a trend to their reduction observed in the hemispheric cortex. Lysosomal hydrolases were activated in the said parts of the brain, their fraction was isolated in percoll gradient 30 min after resuscitation. In lysosomal fraction isolated from cardiac and hepatic tissues at the same period no activation of acid phosphatase and cathepsin D was observed in comparison with the control. It may be assumed that activation of lysosomal enzymes is governed by CN deficit.
 ...
PMID:[Contents of cyclic nucleotides and activity of lysosomal enzymes in heart, brain and liver tissues in the early postresuscitation period]. 789 71

The lysosomal destabilization that precedes mitochondrial apoptotic changes is an important step in cell death, particularly in oxidative cell death. This study describes the novel pharmacological effects of zaprinast, a cGMP-elevating phosphodiesterase inhibitor, on the inhibition of oxidative cell death in astrocyte cultures. H2O2-induced oxidative cytotoxicity was measured grossly by monitoring lactate dehydrogenase (LDH) release, and was found to be associated with lysosomal acridine orange relocation, lysosomal cathepsin D release into cytosol, and reduced mitochondrial potentials. Moreover, zaprinast (100 microM) inhibited all of these cytotoxic phenomena. In addition, H2O2-induced LDH release was not inhibited by 8-pCPT-cGMP, and the inhibition of this release by zaprinast was unaffected by Rp-8-pCPT-cGMP, a protein kinase G inhibitor. Zaprinast was found to inhibit sphingosine-induced lysosomal acridine orange relocation and the induced decrease in mitochondrial potential, but zaprinast had no effect on rotenone-induced mitochondrial collapse, which was not associated with lysosomal destabilization. However, zaprinast did not inhibit the cellular increase of reactive oxygen species induced by H2O2, which suggests that its protective mechanism differs from that of desferrioxamine, which does inhibit such cellular increase of oxygen free radicals. We suggest that the novel protective effect of zaprinast on H2O2-induced oxidative cell death is primarily associated with its inhibition of lysosomal destabilization.
 ...
PMID:Zaprinast inhibits hydrogen peroxide-induced lysosomal destabilization and cell death in astrocytes. 1764 12