Disease relevance of DNASE2

• 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 [1].
• Effect of human polymorphonuclear and mononuclear leukocytes on chromosomal and plasmid DNA of Escherichia coli. Role of acid DNase [2].
• High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents [3].
• DNL was significantly higher before and after meal intake in the overweight men and was positively associated with fasting serum glucose and insulin concentrations [4].
• In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations [5].

Psychiatry related information on DNASE2

• RESULTS: The fractional contribution from DNL to VLDL-triacylglycerol palmitate rose after alcohol consumption from 2 +/- 1% to 30 +/- 8%; nevertheless, the absolute rate of DNL (0.8 g/6 h) represented <5% of the ingested alcohol dose; 77 +/- 13% of the alcohol cleared from plasma was converted directly to acetate entering plasma [6].

High impact information on DNASE2

• Fractional de novo hepatic lipogenesis (DNL) increased more than 10-fold on surplus CHO and was unmeasurable on deficient CHO diets; thus, the preceding 5-d CHO intake could be inferred from DNL [7].
• Although we observed no DNA degradation during phagocytosis by polymorphonuclear leukocytes, lysates of both polymorphonuclear and mononuclear leukocytes contained acid-DNase activity with a pH optimum of 4 [2].
• The subcellular location of acid DNAse in DMSO-induced HL-60 cells was similar to that of monocytes in having a bimodal distribution on fractionated sucrose density gradients [8].
• The increasing capacity to digest DNA during maturation was associated with the development of acid DNAse activity, measured in a cell-free system, and slightly preceded development of 12-O-tetradecanoyl phorbol 13-acetate-stimulated respiratory burst activity [8].
• The acid DNAse had a pH optimum of 5.0 and did not require the presence of calcium or 2-mercaptoethanol (2-ME) [8].

Chemical compound and disease context of DNASE2

• Free fatty acid release during the euglycemic hyperinsulinemic clamp tended to be higher in ESRD and peritoneal dialysis compared to controls (P= 0.08 by ANOVA), while DNL and fractional cholesterol synthesis were normal [9].
• Hydroxycitrate (HCA), a popular dietary supplement for weight loss, is a competitive inhibitor of ATP-citrate lyase, an extramitochondrial enzyme involved in the initial steps of de novo lipogenesis (DNL) [10].

Biological context of DNASE2

• DNase II is ubiquitously expressed in human tissues, and the DNase II gene (DNASE2) was assigned to chromosome 19 [11].
• Recently obtained information on the cDNA encoding human deoxyribonuclease II (DNase II) (T. Yasuda et al., 1998, J. Biol. Chem. 273, 2610-2616) has made it possible to demonstrate the precise position of the the human DNase II gene (DNASE2) on human chromosomes [12].
• The distribution of the activities of both enzymes displayed clear-cut bimodality and the Japanese study population could be classified into two distinct types, namely low-activity (DNASE2 L) and high-activity (DNASE2 H), which indicates the existence of a genetic polymorphism in the activity levels of urinary and leukocytic DNase IIs [13].
• The family study results were compatible with the model that the low activity type is due to an autosomal recessive gene, which indicates that DNASE2 L represents homozygosity for DNASE2*L and DNASE2 H corresponds to homozygosity for DNASE2*H and heterozygosity for DNASE2*L and DNASE2*H [13].
• 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 [1].

Anatomical context of DNASE2

• The enzymatic pathway for synthesis of fatty acids from acetyl-coenzyme A, or de novo lipogenesis (DNL), is present in human liver and, to a lesser extent, in adipose tissue [14].
• Furthermore, postprandial DNL was positively correlated with body fat mass, EE, and triacylglycerol [4].
• Recent studies have demonstrated that acute CHO overfeeding influences adipose tissue lipogenic gene expression and that CHO may stimulate DNL in skeletal muscles, at least in vitro [15].
• The role of DNL and its importance in health and disease remain to be further clarified, in particular the putative effect of DNL on the control of energy intake and energy expenditure, as well as the occurrence of DNL in other tissues (such as in myocytes) in addition to hepatocytes and adipocytes [15].
• It is our hypothesis that DNL plays an important physiologic role in adapting to exclusive breast milk (EBM) feeding or to parenteral nutrition (PN) [16].

Associations of DNASE2 with chemical compounds

• 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 [1].
• Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity [3].
• Hepatic DNL was increased approximately 10-fold in ob/ob mice, whereas hepatic cholesterol synthesis was not affected [17].
• However, after the low-fat, high-carbohydrate diet, triacylglycerols increased significantly and DNL was 5-6-fold higher than in normoinsulinemic subjects consuming a high-fat diet [18].
• CONCLUSION: These data confirm the acute stimulation of DNL after meals in healthy subjects and validate the contribution of this pathway to elevations in triacylglycerol concentration [19].

Other interactions of DNASE2

• Chromosomal localization of a human deoxyribonuclease II gene (DNASE2) to 19p13.2-p13.1 using both the polymerase chain reaction and fluorescence in situ hybridization analysis [12].
• Although a recombinant protein for the putative human DLAD has a divalent cation-independent acid DNase activity, expression of the DLAD mRNA containing the entire open reading frame was not detected in any human tissues tested, except for lung, in which a short 1.1 kb transcript lacking the first two exons is expressed [20].
• DNAS1L2, a member of the DNase I-like endonuclease family, is the only divalent cation-dependent acid DNase so far identified in mammals [21].

Analytical, diagnostic and therapeutic context of DNASE2

• We suggest that a dyad-symmetric DNL IV.XRCC4 tetramer bridges the two ends of the broken DNA and catalyzes the coordinate ligation of the two DNA strands [22].
• DESIGN: After 5 d of an isoenergetic high-fat, low-carbohydrate diet, fasting DNL was measured in normoinsulinemic (<or= 85 pmol/L) lean (n = 9) and obese (n = 6) and hyperinsulinemic (>or= 115 pmol/L) obese (n = 8) subjects [18].
• Glucose metabolism and hepatic DNL were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate [5].
• BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a possible fate of carbohydrate administered during nutritional support [5].
• During the fasting and postprandial periods, serum insulin, glucose, triacylglycerol, and nonesterified fatty acid concentrations were measured, and rates of DNL were quantified via intravenous infusion of [1-(13)C] sodium acetate and mass isotopomer distribution analysis [19].

References