Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.22.1 (DNase II)
429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An acid deoxyribonuclease was extracted from Euglena gracilis SM-ZK, a chloroplast-lacking strain, by homogenizing the cells in 50 mM sodium acetate (pH 4.6). The enzyme was then purified by heat treatment and a series of chromatographic separations. The molecular mass of the Euglena acid DNase was estimated to be 45 kDa by sensitive activity staining in an SDS-polyacrylamide gel using SYBR Green. Treatment of the Euglena enzyme with a reducing agent prior to electrophoresis destroyed its DNase activity in the gel, indicating that disulfide bridging is essential for its enzyme activity. Nucleolytic properties of this enzyme are essentially the same as to those of porcine DNase II. The Euglena enzyme acts on both double-stranded (ds) and single-stranded DNA, but acts preferentially on dsDNA with an optimum pH at approximately 5.3. EDTA did not inhibit its enzyme activity. Euglena DNase makes double-strand breaks in circular DNA substrate and generates a terminus with 3'-phosphate and 5'-OH. These results indicate that the Euglena acid DNase is in fact a member of the DNase II family.
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PMID:Deoxyribonuclease II purified from Euglena gracilis SM-ZK, a chloroplast-lacking mutant: comparison with porcine spleen deoxyribonuclease II. 1195 34

Vitamin C (VC) and vitamin K(3) (VK(3)) administered in a VC:VK(3) ratio of 100:1 exhibit synergistic antitumor activity and preferentially kill tumor cells by autoschizis, a novel type of necrosis characterized by exaggerated membrane damage and progressive loss of organelle-free cytoplasm through a series of self-excisions. During this process, the nucleus becomes smaller, cell size decreases one-half to one-third of its original size, and most organelles surround an intact nucleus in a narrow rim of cytoplasm. While the mitochondria are condensed, tumor cell death does not result from ATP depletion. However, vitamin treatment induces a G(1)/S block, diminishes DNA synthesis, increases H(2)O(2) production, and decreases cellular thiol levels. These effects can be prevented by the addition of catalase to scavenge the H(2)O(2). There is a concurrent 8- to 10-fold increase in intracellular Ca(2+) levels. Electrophoretic analysis of DNA reveals degradation due to the caspase-3-independent reactivation of deoxyribonuclease I and II (DNase I, DNase II). Redox cycling of the vitamins is believed to increase oxidative stress until it surpasses the reducing ability of cellular thiols and induces Ca(2+) release, which triggers activation of Ca(2+)-dependent DNase and leads to degradation of DNA. Recent experiments indicate that oral VC:VK(3) increases the life-span of tumor-bearing nude mice and significantly reduces the growth rate of solid tumors without any significant toxicity by reactivating DNase I and II and inducing autoschizis. This report discusses the mechanisms of action employed by these vitamins to induce tumor-specific death by autoschizis.
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PMID:Autoschizis: a novel cell death. 1203 62

The levels of DNA, RNA, protein and acid and alkaline DNase were studied in developing and old chick cerebellum. The in vitro synthesis of DNA, by both chick cerebrum and cerebellum was also studied, by following the incorporation of [3H]thymidine into DNA. It was observed that the increase in DNA content of chick cerebellum continued well beyond adult stages of life span. Maximal DNA synthesis, as judged by the [3H]thymidine incorporation, was noticed during the early embryonic development but decreased with advancement of age. There was, however, another peak of activity, although smaller, at about 9 months of age. Both cerebrum and cerebellum showed similar patterns. The highest specific activity of acid DNase was also found during the early period of cerebellar development, that is at a time when rapid cellular proliferation was occurring. The activity steadily declined with the aging and in 2-year-old cerebellum very little activity could be detected. Alkaline DNase, on the other hand, not only exhibited high activity during the early development but also remained at a significant level even in old cerebellum. It is concluded that acid DNase shows a positive correlation to the early embryonic DNA synthesis but not to the cell increase occurring in old age.
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PMID:Studies on the synthesis and degradation of DNA in developing and old chick cerebellum. 1217 Jun 8

DNase II alpha (EC 3.1.22.1) is an endonuclease, which is active at low pH, that cleaves double-stranded DNA to short 3'-phosphoryl oligonucleotides. Although its biochemistry is well understood, its structure-activity relationship has been largely unexamined. Recently, we demonstrated that active DNase II alpha consists of one contiguous polypeptide, heavily glycosylated, and containing at least one intrachain disulphide linkage [MacLea, Krieser and Eastman (2002) Biochem. Biophys. Res. Commun. 292, 415-421]. The present paper describes further work to examine the elements of DNase II alpha protein required for activity. Truncated forms and site-specific mutants were expressed in DNase II alpha-null mouse cells. Results indicate that the signal-peptide leader sequence is required for correct glycosylation and that N-glycosylation is important for formation of the active enzyme. Despite this, enzymic deglycosylation of wild-type protein with peptide N-glycosidase F reveals that glycosylation is not intrinsically required for DNase activity. DNase II alpha contains six evolutionarily conserved cysteine residues, and mutations in any one of these cysteines completely ablated enzymic activity, consistent with the importance of disulphide bridging in maintaining correct protein structure. We also demonstrate that a mutant form of DNase II alpha that lacks the purported active-site His(295) can still bind DNA, indicating that this histidine residue is not simply involved in DNA binding, but may have a direct role in catalysis. These results provide a more complete model of the DNase II alpha protein structure, which is important for three-dimensional structural analysis and for production of DNase II alpha as a potential protein therapeutic for cystic fibrosis or other disorders.
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PMID:Structural requirements of human DNase II alpha for formation of the active enzyme: the role of the signal peptide, N-glycosylation, and disulphide bridging. 1255 98

Deoxyribonuclease IIalpha (DNase IIalpha) is an acidic endonuclease found in lysosomes and nuclei, and it is also secreted. Though its Caenorhabditis elegans homolog, NUC-1, is required for digesting DNA of apoptotic cell corpses and dietary DNA, it is not required for viability. However, DNase IIalpha is required in mice for correct development and viability, because undigested cell corpses lead to lesions throughout the body. Recently, we showed that, in contrast to previous reports, active DNase IIalpha consists of one contiguous polypeptide. To better analyze DNase II protein structure and determine residues important for activity, extensive database searches were conducted to find distantly related family members. We report 29 new partial or complete homologs from 21 species. Four homologs with differences at the purported active site histidine residue were detected in the parasitic nematodes Trichinella spiralis and Trichinella pseudospiralis. When these mutations were reconstructed in human DNase IIalpha, the expressed proteins were inactive. DNase II homologs were also identified in non-metazoan species. In particular, the slime-mold Dictyostelium, the protozoan Trichomonas vaginalis, and the bacterium Burkholderia pseudomallei all contain sequences with significant similarity and identity to previously cloned DNase II family members. We report an analysis of their sequences and implications for DNase II protein structure and evolution.
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PMID:A family history of deoxyribonuclease II: surprises from Trichinella spiralis and Burkholderia pseudomallei. 1259 37

During polyspermic fertilisation in birds numerous spermatozoa enter the eggs, in contrast to the situation in mammals where fertilisation is monospermic. However, in birds only one of the spermatozoa which have entered an egg participates in zygote nucleus formation, while the supernumerary spermatozoa degenerate at early embryogenesis. Our previous work has demonstrated the presence in preovulatory quail oocytes of DNase I and II activities able to digest naked lambdaDNA/HindIII substrate in vitro. In the present studies, the activities of both DNases in quail oocytes at different stages of oogenesis and in ovulated mouse oocytes were assayed in vitro using the same substrate. Degradation of quail spermatozoa by quail oocyte extracts was also checked. Digestion of the DNA substrate was evaluated by electrophoresis on agarose gels. The activities of DNase I and II in quail oocytes increased during oogenesis and were the highest in mature oocytes. The activities were present not only in germinal discs but also in a thin layer of cytoplasm adhering to the perivitelline layer surrounding the yolk. At all stages of oogenesis the activity of DNase II was much higher than that of DNase I. DNA contained in spermatozoa was also degraded by the quail oocyte extracts under conditions optimal for both DNases. In contrast to what is observed in quail oocytes, no DNase activities were detected in ovulated mouse eggs; this is logical as they would be useless or even harmful in monospermic fertilisation. The possible role of DNase activities in avian oocytes, in degradation of accessory spermatozoa during polyspermic fertilisation, is discussed.
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PMID:DNase I and II present in avian oocytes: a possible involvement in sperm degradation at polyspermic fertilisation. 1262 27

L-DNase II is derived from its precursor leucocyte elastase inhibitor (LEI) by post-translational modification. In vitro, the conversion of LEI into L-DNase II can be induced by incubation of LEI at an acidic pH. In this study, we proposed to analyze the effects of intracellular acidification on this transformation. Amiloride derivatives, like hexamethylene amiloride (HMA), are known to provoke a decrease of cytosolic pH by inhibiting the Na(+)/H(+) antiport. In BHK cells, treatment with HMA-induced apoptosis accompanied by an increase in L-DNase II immunoreactivity and L-DNase II enzymatic activity. Overexpression of L-DNase II precursor led to a significant increase of apoptosis in these cells supporting the involvement of L-DNase II in HMA induced apoptosis. As previously shown in other cells, etoposide-induced apoptosis did not activate L-DNase. On the contrary, LEI overexpression significantly increased cell survival in etoposide-induced apoptosis. Together these results suggest differential roles of LEI and L-DNase II in response to different types of apoptotic inducers.
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PMID:Apoptosis induced by Na+/H+ antiport inhibition activates the LEI/L-DNase II pathway. 1272 53

1. Exposure of isolated liver mitochondria to high doses of gamma rays from a Co(60) source causes the level of DNase II activity to increase. Treatment of the mitochondria with sonic vibration causes a further elevation of the activity to a level which is independent of the prior radiation dose. 2. Such increased mitochondrial DNase II activity appears to be due to the "structural damage" of the subcellular particulates caused by the ionizing radiation. Other methods of disrupting the mitochondrial structure also cause increased DNase II activity. A causal relationship between the structural alteration and the increased enzymatic activity is postulated. 3. The DNase II activity appears to be closely associated with the structural elements of the mitochondria and remains associated with the fragments after irradiation. 4. Upon irradiation, the mitochondrial suspension releases ultraviolet-absorbing materials which are probably nucleotide in nature. 5. The possibility of localization of DNase activity in the lysosome fraction of de Duve (15) is discussed. It is felt that DNase II is at least in part a mitochondrial enzyme and that probably the conclusions drawn here would be applicable to any DNase II present in the lysosomes as well. 6. Irradiation of whole liver homogenate causes no increased DNase II activity. The experiments do not provide any information on the presence or action of protective substances in the homogenate.
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PMID:Effect of gamma irradiation on the desoxyribonuclease II activity of isolated mitochondria. 1343 7

The anthelmintic fenbendazole (FBZ) induces nuclear DNA fragmentation (DF) in intestinal cells of Haemonchus contortus. The DNA fragments had 3'-OH, which suggests involvement of a neutral DNase. To identify candidate DNase(s) involved, DNase activity in H. contortus intestine and other worm fractions was characterized relative to classic DNases I (neutral) and II (acidic). Seven distinct DNase activities were identified and had Mrs of 34, 36, 37 or 38.5 kDa on zymographic analysis. The different activities were distinguished according to pH requirement, sensitivity to 10 mM EDTA and worm compartment. Activities of intestinal DNases at 34, 36 and 38.5 kDa were sensitive to EDTA at pH 5.0 and 7.0. Sensitivity to EDTA at pH 5.0 was unexpected compared to classic acidic DNase II activity, suggesting unusual properties of these DNases. In whole worms, however, the activities at 36 and 38.5 kDa were relatively insensitive to EDTA, indicating predominance of DNases that are distinct from the intestine. The activity at 37 kDa in excretory/secretory products had an acidic pH requirement and was insensitive to EDTA, resembling classic acidic DNase activity. Under conditions of pH 5.0 and 7.0, intestinal DNases produced 3'-ends that could be labeled by terminal deoxynucleotidyl transferase, indicating presence of 3'-OH. The labeling of 3'-ends at pH 5.0, again, was unexpected for acidic DNase activity. These results and several other activities suggest that multiple H. contortus DNases have characteristics distinct from the classic mammalian DNases I and II. Treatment of H. contortus with FBZ did not induce any detectable DNase activities distinct from normal intestine, although relative activities of intestinal DNases appear to have been altered by this treatment.
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PMID:Non-classic characteristics define prominent DNase activities from the intestine and other tissues of Haemonchus contortus. 1455 60

The effect of various toxic compounds (phenol, gasoline, detergents, halogenated benzenes, and copper salts) on the activity and multiple forms of acid DNase was investigated in the liver of the widespread freshwater snail species Viviparus viviparus L. Characteristic variations in the specific activity and isoform pattern of the enzyme depending on pollutant concentration and exposure time were revealed. It was shown that the pattern of DNase isoforms in V. viviparus could be an index of water pollution.
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PMID:[Effect of industrial toxic pollutants on the activity and isoforms of acid DNase in the freshwater snail (Viviparus viviparus L.)]. 1459 63


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