Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of repeated (20 days) exposure to picrotoxin (PTX) on rat liver lysosomal function was evaluated by measuring the free and total activities of acid phosphatase, cathepsin D, ribonuclease II (RNAse II) and deoxyribonuclease II (DNAse II). The free activities of the nucleases (both RNAse II and DNAse II) were increased following PTX exposure. The total DNAse II activity was increased by 2.2-fold whereas the total acid phosphatase activity was decreased by 28%. Consequently, the ratios of total activity / free activity were low in the PTX exposed groups, implying loss of membrane integrity. Cathepsin D activity was completely abolished. The results show that repeated exposure to PTX can lead to lysosomal dysfunction in liver.
 ...
PMID:Effect of repeated intraperitoneal exposure to picrotoxin on rat liver lysosomal function. 1557 32

We determined whether recombinant human growth hormone (rhGH) administration might modulate the enzyme degradative capacity of the muscle lysosomal system and influence muscle growth. Muscle cathepsin D, acid RNase and DNase II activities are determined in the gastrocnemius muscle of rhGH-treated post-weaning female BALB/c mice. Linear regressions were used to analyze the relationships of each enzyme with their respective substrate. GH induced a depletion-recovery response of muscle growth through a mechanism which is similar to catch-up growth. In these conditions, cathepsin D activity decreased with age in all animals (GH: 40%; saline: 79%), showing a substantial developmental decline that could reflect changes in the rate of protein breakdown. However, the degradative capacity of cathepsin D was paradoxically unmodified in rhGH-mice compared with saline mice (according to the enzyme vs. substrate linear regression slope), in spite of the increase in enzyme activity elicited by GH. This suggests that the muscle protein breakdown is not increased by GH-treatment in post-weaning mice. The enhancement of muscle protein deposition as indicated by the augmented muscle cell size (protein:DNA ratio) of rhGH-mice (increased 178% from 25 to 50 days) vs. saline, can be attributed to a higher muscle K(RNA). In contrast, acid RNase and DNase II activities directly participate in muscle RNA and DNA degradation. Both nucleases were inhibited by GH treatment (a decrease of 48% and 63%, respectively, vs. saline at 50 days). The decrease in RNase activity suggests an inverse relation between the rate of protein synthesis (high) and acid RNase activity (low), leading to spare muscle RNA for synthesizing protein during catch-up growth. Also, low DNase II activity could contribute to inhibiting of muscle DNA degradation, facilitating muscle growth. Thus, GH seems to act as a direct modulator of the degradative capacity of skeletal muscle nucleases but not of cathepsin D, influencing DNA and RNA degradation during the depletion-recovery response to GH of gastrocnemius muscle in female post-weaning mice.
 ...
PMID:Growth hormone modulates the degradative capacity of muscle nucleases but not of cathepsin D in post-weaning mice. 1749 91

LEI (Leukocyte Elastase Inhibitor), the precursor of the pro-apoptotic molecule L-DNase II, belongs to the ovalbumin subgroup of serpins. Several serpins can inhibit apoptosis: the viral serpin Crm A inhibits Fas or TNFalpha-induced apoptosis, and overexpression of PAI-2 or PI-9 protects cells from TNFalpha or granzyme B induced apoptosis. We have previously shown that LEI overexpression protects cells from etoposide-induced apoptosis. The molecular reason of this anti-apoptotic activity is now investigated. We show that, in BHK-21 and HeLa cells, LEI anti-protease activity is essential for its anti-apoptotic effect. The protease inhibited is cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis. This let us presume that high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent.
 ...
PMID:Leukocyte Elastase Inhibitor, the precursor of L-DNase II, inhibits apoptosis by interfering with caspase-8 activation. 1867 71

Neuroprotection strategies in the retina aim at interference with regulatory mechanisms of cell death. To successfully target these mechanisms it is necessary to understand the molecular pathways activated in the degenerating retina. Induced retinal degeneration models, like the light damage model, give a synchronized response allowing their detailed investigation. In this study we exposed Fisher rats to a continuous white light. This induced a caspase-independent cell death in which the activation of cathepsin D has an important role via the activation of L-DNase II. Inhibition of this enzyme by intravitreal administration of pepstatin A protects photoreceptors indicating that this enzyme might be an interesting target for neuroprotection.
 ...
PMID:Light induced retinal degeneration activates a caspase-independent pathway involving cathepsin D. 2055 23

Effects of treatmentin vivo with the antimalarials:chloroquine (CQ), primaquine (PQ) and quinine(Q) on lysosomal enzymes and lysosomal membrane integrity were examined. Treatment with the three antimalarials showed an apparent increase in the membrane stability. CQ treatment resulted in increase in both the 'free' and 'total' activities of all the enzymes i.e. acid phosphatase, RNase II, DNase II and cathepsin D. PQ treatment lowered the 'free' and 'total' activities of acid phosphatase and cathepsin D, but the DNase II activities increased. Treatment with Q resulted in increased 'free' and 'total' activities of RNase II and DNase II. While 'free' activities of acid phosphatase and cathepsin D were low; the 'total' activities increased significantly. Our results suggest that a generalized increase in free nucleases activities following prolonged treatment with antimalarials may lead to cell damage and/or necrosis.
 ...
PMID:Effect of antimalarials treatment on rat liver lysosomal function-Anin vivo study. 2310 85

The effect of picrotoxin-induced convulsions on lysosomal function in rat brain were evaluated by measuring the free as well as total acid phosphatase, cathepsin D, acid ribonuclease (RNAse II) and acid deoxyribonuclease (DNAse II) activities. Following picrotoxin treatment the free RNAse II activity increased whereas the total activities of practically all the other enzymes decreased. Paradoxically, the cathepsin D activity, free as well the total was completely abolished. In case of all the enzymes the ratio of Total activity/Free activity decreased indicating increased lysosomal membrane fragility which could lead to process of neurodegeneration in the epileptic animals.
 ...
PMID:Picrotoxin-induced convulsions and lysosomal function in the rat brain. 2310 95

In light induced retinal degeneration (LIRD) photoreceptor cell death is mediated by caspase independent mechanisms. The activation of LEI/L-DNase II pathway in this model, is due to cathepsin D release from lysosomes, although the underlying mechanism remains poorly understood. In this paper we studied the involvement of calpains in lysosomal permeabilization. We investigated, for the first time, the calpain targets at lysosomal membrane level. We found that calpain 1 is responsible for lysosomal permeabilization by cleavage of the lysosomal associated membrane protein 2 (LAMP 2). Moreover, LAMP 2 degradation and lysosomal permeabilization were rescued by calpain inhibition and the use of MEF(-/-)lamp 2 cells indicates that the cleavage of LAMP 2A is essential for this permeabilization. Finally, we found that LAMP 2 is cleaved in LIRD, suggesting that the mechanism of calpain induced lysosomal permeabilization is not exclusive of a single cell death model. Overall, these data shed new light on understanding the mechanisms of lysosomal and caspase-independent cell death and point to the original targets for development of the new therapeutic protocols.
...
PMID:Calpain 1 induce lysosomal permeabilization by cleavage of lysosomal associated membrane protein 2. 2374 42

Lysosomes contain hydrolytic enzymes that can degrade proteins and DNA. Leakage of these reactive compounds through a compromised lysosomal membrane causes lysosomal cell death, which can have apoptotic, necrotic, or mixed morphology. Lysosomal cathepsin proteases, such as cathepsin D, and the lysosomal endonuclease, DNase II, have both been implicated in lysosome-related cell death. Here, we present a fluorescence dual-labeling technique for simultaneous visualization of these two markers of lysosomal activity linked to cell death. The approach labels the intracellular distribution of cathepsin D and the sites with DNase II-type breaks in fixed tissue sections. It determines the lysosomal or extra-lysosomal localization of the markers and can be useful in studying pathways and signals of lysosomal cell death.
 ...
PMID:Dual Detection of Nucleolytic and Proteolytic Markers of Lysosomal Cell Death: DNase II-Type Breaks and Cathepsin D. 2818 96


<< Previous 1 2