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an enzyme produced by some hemolytic strains of streptococcus that dissolves fibrinous secretions from infections; used medicinally (often in combination with streptokinase)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/14 23:15:49」(JST)

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Crystals of a DNase protein.

A deoxyribonuclease (DNase, for short) is any enzyme that catalyzes the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading DNA. Deoxyribonucleases are one type of nuclease, a generic term for enzymes capable of hydrolising phosphodiester bonds that link nucleotides. A wide variety of deoxyribonucleases are known, which differ in their substrate specificities, chemical mechanisms, and biological functions.

Modes of action

Some DNases cut, or "cleave", only residues at the ends of DNA molecules (exodeoxyribonucleases, a type of exonuclease). Others cleave anywhere along the chain (endodeoxyribonucleases, a subset of endonucleases).

Some are fairly indiscriminate about the DNA sequence at which they cut, while others, including restriction enzymes, are very sequence-specific.

Some cleave only double-stranded DNA; others are specific for single-stranded molecules; and still others are active toward both.

DNase enzymes can be inhaled using a nebuliser by cystic fibrosis sufferers. DNase enzymes help because white blood cells accumulate in the mucus, and, when they break down, they release DNA, which adds to the 'stickiness' of the mucus. DNase enzymes break down the DNA, and the mucus is much easier to clear from the lungs.

Uses of deoxyribonucleases

Intrapleural tissue plasminogen activator (tPA) combined with deoxyribonuclease has been shown to increase pleural drainage, decrease hospital length of stay, and decrease need for surgery in parapneumonic effusions and empyema.

The studied protocol used a dose of DNase (Pulmozyme, Roche) of 5 mg, and a dose of t-PA (Actilyse, Boehringer Ingelheim) of 10 mg. Intrapleural medications are each given twice daily for 3 days, and each administration was followed by clamping of the drain to permit the drug to remain in the pleural space for 1 hour. Treatment with DNase alone or t-PA alone was ineffective.^[1]

Types of deoxyribonucleases

The two main types of DNase found in metazoans are known as deoxyribonuclease I and deoxyribonuclease II.

Other types of DNase include Micrococcal nuclease.

Assay of deoxyribonucleases

DNA absorbs UV light with a wavelength of maximal absorbance near 260 nm. This absorption is due to the pi electrons in the aromatic bases of the DNA. In dsDNA, or even regions of RNA where double-stranded structure occurs, the bases are stacked parallel to each other, and the overlap of the base molecular orbitals leads to a decrease in absorbance of UV light. This phenomenon is called the hypochromic effect. When DNAse liberates nucleotides from dsDNA, the bases are no longer stacked as they are in dsDNA, so that orbital overlap is minimized and UV absorbance increases. This increase in absorbance underlies the basis of Kunitz unit of DNAse activity. One Kunitz unit is defined as the amount of enzyme added to 1 mg/ml salmon sperm DNA that causes an increase in absorbance of 0.001 per minute at the wavelength of 260 nm when acting upon highly polymerized DNA at 25 ºC in a 0.1 M NaOAc (pH 5.0) buffer. The unit's name recognizes the Russian-American biochemist M. Kunitz, who proposed the standard test in 1946.

A standard enzyme preparation should be run in parallel with an unknown because standardization of DNA preparations and their degree of polymerization in solution is not possible.

Notes and references

^ Rahman, Najib (August 11, 2011). "Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection". The New England Journal of Medicine (365): 518–526. doi:10.1056/NEJMoa1012740.

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5. A群レンサ球菌：病原性因子および発症機序 group a streptococcus virulence factors and pathogenic mechanisms

English Journal

Mapping nucleosome positions using DNase-seq.

Zhong J1, Luo K1, Winter PS1, Crawford GE1, Iversen ES1, Hartemink AJ2.
Genome research.Genome Res.2016 Jan 15. pii: gr.195602.115. [Epub ahead of print]
As the fundamental units of chromatin, nucleosomes contribute to virtually all aspects of genome function. Common methods for mapping nucleosome positions rely on genome cleavage using micrococcal nuclease (MNase), or more recently, genetically-modified histones. Though deoxyribonuclease I (DNase I)
PMID 26772197

Deoxyribonuclease I gene polymorphism and susceptibility to systemic lupus erythematosus.

Mohammadoo-Khorasani M1,2, Musavi M3, Mousavi M4, Moossavi M5, Khoddamian M6, Sandoughi M7, Zakeri Z7.
Clinical rheumatology.Clin Rheumatol.2016 Jan;35(1):101-5. doi: 10.1007/s10067-015-3111-y. Epub 2015 Nov 7.
The DNASE1 gene is regarded as one of the susceptible genes for systemic lupus erythematosus (SLE). Recent studies have detected the presence of a variable number of tandem repeat (VNTR) polymorphisms at intron 4 in this gene. The current study aimed to investigate the influence of current polymorph
PMID 26547219

Neutrophil Toll-Like Receptor 9 Expression and the Systemic Inflammatory Response in Acetaminophen-Induced Acute Liver Failure.

Manakkat Vijay GK1, Ryan JM, Abeles RD, Ramage S, Patel V, Bernsmeier C, Riva A, McPhail MJ, Tranah TH, Markwick LJ, Taylor NJ, Bernal W, Auzinger G, Willars C, Chokshi S, Wendon JA, Ma Y, Shawcross DL.
Critical care medicine.Crit Care Med.2016 Jan;44(1):43-53. doi: 10.1097/CCM.0000000000001309.
OBJECTIVES: There is a marked propensity for patients with acetaminophen-induced acute liver failure to develop sepsis, which may culminate in multiple organ failure and death. Toll-like receptors sense pathogens and induce inflammatory responses, but whether this is protective or detrimental in ace
PMID 26457748

Japanese Journal

Effect of Varidase (streptodornase) on biofilm formed by Pseudomonas aeruginosa

CHEMOTHERAPY 49(3), 121-125, 2003
NAID 120004211197

左肺全摘後気管支断端瘻および MRSA 膿胸に対し保存的治療を行った1例

日本外科系連合学会誌 27(4), 646-649, 2002-08-30
NAID 10010035811

D-19 結核性胸膜炎後の膿胸, 胸囲結核, 対側肺結核に対する保存的治療 : streptokinase-streptodornase洗浄を含む

気管支学 : 日本気管支研究会雑誌 23(3), 252, 2001-04-25
NAID 110002814638

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