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DNase II (dnase + ii)

Distribution by Scientific Domains
Chemistry66%
Medical Sciences33%

Selected Abstracts

IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradation

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008
Yasutaka Okabe
Abstract DNase II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. Macrophages in DNase II-deficient mice accumulate undigested DNA and constitutively produce IFN-, as well as TNF-,. The IFN-, causes severe anemia in the DNase II,/, embryos, which die prenatally. On the other hand, when the DNase II gene is inactivated postnatally, mice develop polyarthritis owing to the TNF-, produced by macrophages. Here, we showed that the IFN-, gene activation in DNase II,/, mice is dependent on IFN regulatory factor (IRF) 3 and 7. Accordingly, DNase II,/,IRF3,/,IRF7,/, mice do not suffer from anemia, but they still produce TNF-,, and age-dependently develop chronic polyarthritis. A microarray analysis of the gene expression in the fetal liver revealed a set of genes that is induced in DNase II,/, mice in an IRF3/IRF7-dependent manner, and another set that is induced independent of these factors. These results indicate that the mammalian chromosomal DNA that accumulates in macrophages due to inefficient degradation activates genes in both IRF3/IRF7-dependent and -independent manners. [source]

Sp1 and Sp3 are involved in up-regulation of human deoxyribonuclease II transcription during differentiation of HL-60 cells

FEBS JOURNAL, Issue 8 2003
San-Fang Chou
Expression of DNase II in macrophages is potentially crucially important in the removal of unwanted DNA. We have previously shown that DNase II expression is up-regulated at the transcriptional level during the phorbol 12-myristate-13-acetate (PMA)-induced differentiation of HL-60 and THP-1 cells. In this study, we investigated the cis -regulatory elements and transcription factors involved in this process in HL-60 cells. cis -Regulatory elements in the DNase II promoter were located by 5, deletion and site-directed mutagenesis of promoter-luciferase constructs and transient transfection of HL-60 cells. Furthermore, the binding proteins were identified by electrophoretic mobility shift assay (EMSA) in the presence of specific antibodies. In the DNase II promoter, 249 base pairs upstream of the transcription start site were essential for maximal promoter activity in both untreated and PMA-treated HL-60 cells and, within this region, three Sp1 and Sp3 binding sites were identified as essential for transcriptional regulation and PMA induction. Western blot analysis showed that PMA treatment resulted in increased levels of Sp1 and Sp3 proteins. Furthermore, cotransfection analysis in Drosophila SL2 cells showed that Sp1 was more potent than Sp3 in activating the DNase II promoter. We therefore conclude that Sp1 and/or Sp3 are involved in the up-regulation of DNase II expression during the differentiation of HL-60 cells. [source]

Human lysosomal DNase II, contains two requisite PLD-signature (HxK) motifs: Evidence for a pseudodimeric structure of the active enzyme species

PROTEIN SCIENCE, Issue 1 2007
Patrick Schäfer
Abstract Lysosomal DNase II, is essential for DNA waste removal and auxiliary apoptotic DNA fragmentation in higher eukaryotes. Despite the key role of this enzyme, little is known about its structure,function relationships. Here, mutational and biochemical analyses were used to characterize human DNase II, variants expressed in mammalian cells. The resulting data strongly support the hypothesis that the enzyme is a monomeric phospholipase D,family member with a pseudodimeric protein fold. According to our results, DNase II, contains two requisite PLD-signature motifs (113HTK115 and 295HSK297) in the N- and C-terminal subdomains, respectively, that together form a single active site. Based on these data, we present an experimentally validated structural model of DNase II,. [source]

Protective targeting of high mobility group box chromosomal protein 1 in a spontaneous arthritis model

ARTHRITIS & RHEUMATISM, Issue 10 2010
Therese Östberg
Objective High mobility group box chromosomal protein 1 (HMGB-1) is a DNA binding nuclear protein that can be released from dying cells and activated myeloid cells. Extracellularly, HMGB-1 promotes inflammation. Clinical and experimental studies demonstrate that HMGB-1 is a pathogenic factor in chronic arthritis. Mice with combined gene deficiency for DNase II and IFNRI spontaneously develop chronic, destructive polyarthritis with many features shared with rheumatoid arthritis. DNase II is needed for macrophage degradation of engulfed DNA. The aim of this study was to evaluate a potential pathogenic role of HMGB-1 in this novel murine model. Methods The course of arthritis, assessed by clinical scoring and histology, was studied in DNase II,/, × IFNRI,/, mice, in comparison with heterozygous and wild-type mice. Synovial HMGB-1 expression was analyzed by immunohistochemistry. Serum levels of HMGB-1 were determined by Western immunoblotting and enzyme-linked immunosorbent assay (ELISA), and anti,HMGB-1 autoantibodies were detected by ELISA. Macrophage activation was studied by immunostaining for intracellular interleukin-1, and HMGB-1. HMGB-1 was targeted with truncated HMGB-1,derived BoxA protein, acting as a competitive antagonist, with intraperitoneal injections every second day for 5 weeks. Results DNase II,/, × IFNRI,/, mice developed symmetric polyarthritis with strong aberrant cytosolic and extracellular HMGB-1 expression in synovial tissue, in contrast to that observed in control animals. Increased serum levels of HMGB-1 and HMGB-1 autoantibodies were recorded in DNase II,/, × IFNRI,/, mice, both prior to and during the establishment of disease. Systemic HMGB-1,specific blockade significantly ameliorated the clinical disease course, and a protective effect on joint destruction was demonstrated by histologic evaluation. Conclusion HMGB-1 is involved in the pathogenesis of this spontaneous polyarthritis, and intervention with an HMGB-1 antagonist can mediate beneficial effects. [source]