Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.25.1 (deoxyribonuclease)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to single-stranded DNA (anti-ssDNA) and double-stranded DNA (anti-dsDNA) were determined in serum and urine of nine patients with systemic lupus erythematosus (SLE) presenting with heavy proteinuria (greater than 300 mg/dl), and the activity of anti-DNA antibodies was compared between paired serum and urine samples in each patient. The results were expressed by the anti-DNA activity (radioimmunoassay units per milliliter) divided by the concentration of IgG (milligrams per milliliter), so as to correct for the difference of IgG concentration. Anti-DNA was detected invariably in the serum of these patients (anti-ssDNA/IgG 4.8 to 27.2, anti-dsDNA 5.6 to 107.8). In contrast, anti-DNA activity was not detectable in urine samples from any of the nine patients. The urine samples from these patients, as well as those from normal individuals, were found to contain ssDNA at levels not significantly different from each other (0.25 +/- 0.15 vs. 0.19 +/- 0.07 microgram/mg creatinine, P greater than 0.1). The failure to detect anti-DNA in the urine of SLE patients, however, was not due to the ssDNA contained in the urine, because no anti-DNA activity was detected even after their urine samples had been digested with deoxyribonuclease. On the basis of these results, anti-DNA in the serum of SLE patients was considered to be entrapped in the kidney, probably owing to its binding with DNA deposited in their glomeruli.
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PMID:Entrapment of anti-DNA antibodies in the kidney of patients with systemic lupus erythematosus. 698 73

Sepsis is characterized by systemic activation of coagulation and inflammation in response to microbial infection. Although cell-free DNA (cfDNA) released from activated neutrophils has antimicrobial properties, it may also exert harmful effects by activating coagulation and inflammation. The authors aimed to determine whether deoxyribonuclease (DNase) administration reduces cfDNA levels, attenuates coagulation and inflammation, suppresses organ damage, and improves outcome in a cecal ligation and puncture (CLP) model of polymicrobial sepsis. Healthy C57Bl/6 mice were subjected to CLP, a surgical procedure involving two punctures of the ligated cecum, or sham surgery (no ligation/puncture). Mice were given DNase or saline by intraperitoneal injection 2, 4, or 6 h after surgery. Two hours after treatment, organs were harvested and plasma levels of cfDNA, interleukin-6 (IL-6), IL-10, thrombin-antithrombin complexes, lung myeloperoxidase, creatinine, alanine transaminase, and bacterial load were quantified. Survival studies were also performed. The CLP-operated mice had rapid time-dependent elevations in cfDNA that correlated with elevations in IL-6, IL-10, and thrombin-antithrombin complexes and had organ damage in the lungs and kidneys. Administration of DNase at 2 h after CLP resulted in increased IL-6 and IL-10 levels and organ damage in the lungs and kidneys. In contrast, DNase administration at 4 or 6 h after CLP resulted in reduced cfDNA and IL-6 levels, increased IL-10, and suppressed organ damage and bacterial dissemination. Deoxyribonuclease administration every 6 h after CLP also rescued mice from death. Our studies are the first to demonstrate that delayed but not early administration of DNase may be protective in experimental sepsis.
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PMID:Delayed but not Early Treatment with DNase Reduces Organ Damage and Improves Outcome in a Murine Model of Sepsis. 2600 20

Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation, exacerbating liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. This study analyzed the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals. Administration of deoxyribonuclease resulted in a mild, nonsignificant decrease in total plasma DNA and plasma DNA of mitochondrial origin but not of nuclear origin. This was accompanied by a decrease in bilirubin, creatinine, and blood urea nitrogen as markers of renal function. In conclusion, the study confirmed the hepatotoxic and nephrotoxic effect of thioacetamide. The associated increase in cell-free DNA seems to be involved in hepatorenal pathogenesis because treatment with deoxyribonuclease resulted in a partial prevention of hepatorenal injury. Further experiments will focus on the effects of long-term treatment with deoxyribonuclease in other clinically more relevant models. Clinical studies should test endogenous deoxyribonuclease activity as a potential risk determinant for kidney or liver failure.NEW & NOTEWORTHY Thioacetamide-induced hepatorenal injury resulted in higher plasma cell-free DNA. Deoxyribonuclease decreased average cell-free DNA of mitochondrial origin but not nuclear origin. Deoxyribonuclease partially prevented hepatorenal injury in rats.
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PMID:Deoxyribonuclease partially ameliorates thioacetamide-induced hepatorenal injury. 2820 3