DNASES THERAPEUTIC AND BIOCHEMISTRY SIGNIFICANCE

Abstract:

In clinical point of  view, when DNA is degraded this situation becomes critical and it affects healthy life of organisms .

1.      DNAse1 and DNAse2 have greater role in diseases.

2.      In a single DNases family there are various different enzymes that are playing their role in tissues.

3.      Presence of DNase is important though they are not properly characterized but when these DNase families are removed they can cause many diseases.

4.      For the breakdown of DNA , DNase requires Mg2+ and Ca2+.

5.      Ion binding sites that are present in DNase are four in number.

6.      As Ca2+ and Mg2+ are present so, there are two binding sites for Mg2+ and two are for Ca2+.

7.      In this article we will discuss how DNases are important in clinical point of view and what type of biochemical significance they have?

Introduction:

DNases are very important for the survival of humans and many other animals. Presence of DNase is crucial for healthy life of species as their absence lead to many diseases .Two DNase families are present in humans. These are DNAse1 and DNAse2 .Basically these DNases are enzymes and their properties depends on their functions .In case of DNAse1 it requires Mg2+ and Ca2+ and its activity is maximum at Ph7.DNAse1 starts DNA cleavage from 5` end while in case of DNAse2 it does not require Mg2+ and Ca2+.Its activity is maximum at Ph below 7.It starts cleavage of DNA from 3` end. These families contain variety of enzymes that are performing their functions. For mapping purpose of proteins DNases are involved in the treatment of cystic fibrosis. It is also involved in the treatment of cancer and many other diseases. When DNAse1 is added in buffer its activity is reduced. In DNAse1 and 2,Ca2+ contains loops of amino acids and these loops are stabilized by Ca2+.Mg2+ plays greater role in catalysis. Inactive variants are formed when mutations occur in DNAse1.

Therapeutic significance of DNases:

Here we will discuss that how DNases are important in clinical point of view.DNAse1 and DNAse2 are greatly distributed in tissues and their importance in clinical point of view can be observed by evaluating their distribution in tissues.DNAse1 is present in large amount in digestive tract as it contains complex of enzymes.DNAse1 and 2 both are present in blood. Major source of DNAse2 is liver and spleen. Low level of DNAse2 is also present in neurons. In case of skeletal muscles the activity of DNAse2 is restricted. In skin DNAse2 is also restricted. In macrophages amount of DNAse2 is greater.DNAse1 and DNAse2 are greatly distributed in tissues but cell type is limited. In case of structure DNAse1 and 2 have unique structures. As stated earlier that absence of DNase families lead to many diseases. These diseases are as follows:

Lupus erythematosus:

This disease is a complex disease and it is caused because of generation of autoantibody. These antibodies first cause inflammation and they cause damage of organs. Joints and kidneys are most affected by this disease. Absence of DNAse2 causes this disease. Chromatin complexes are not formed in serum and as a result autoantibody are formed that cause this disease. We are greatly protected from the formation of autoantibody because of release of DNAse1 and DNAse2.When DNAse1 is removed it leads to mutation. In patients of lupus erythematosus the activity of DNAse1 is low. When NETs are degraded it prevents the formation of autoantibody and this degradation of NETs is caused by DNAse1.An experiment was performed with mice in which DNAse1 was removed so, mice caught lupus erythematosus. It proved that lupus erythematosus was caused by the absence of DNAse1.Deficiency of DNAse2 causes autoimmunity and also lupus erythematosus but there are two changes associated with this.

These changes are:

·         Deficiency of DNAse2 causes Pediatric onset and does not causes adult onset in case of humans.

·         Deficiency of DNAse2 causes lupus erythematosus and also causes a condition known as HUVS.

 

Symptoms:

Symptoms of HUVS are:

·         Redness of skin because of swelling of capillaries.

·         Lungs obstruction.

·         Serum complement formation.

DNAse2 is necessary in order to prevent autoimmunity. This data shows that the digestion of naked DNA is done by DNAse1 and it causes adult onset while micro particles are digested by DNAe2 and causes pediatric onset.DNAse2 first digests DNA into fragments.DNAse1 digests the chromatin portion of DNA. Both of these DNases require plasminogen system for their regulation. When plasmin is activated than DNAse2 is blocked. DNase 1 is unable to treat lupus nephritis. While DNase 2  therapy might result in successful treatment of lupus nephritis. When DNAse2  is blocked it inhibits the release of 1L-1B Which is released from macrophages. This might delays the activation of immune system. The immune system responses that are being observed during pediatric onset are resulted from inflammosome.

Pompes disease

Causes

This disease is caused by:

·         Deficiency of acid maltose.

·         Glycogen storage.

If it remains untreated than patient may die because it also involves heart diseases. Further information about this disease is unknown. According to some suggestions this disease is caused by DNAse1.Later on, some indications also showed that DNAse1 is not associated with Pompes disease.DNAse1L1 plays greater role in the health of muscles.

Experiment:

An experiment was performed with mice. In mice DNAse1L1 was removed from mice and mice was observed during.

Results:

Mice was when observed it showed two symptoms:

·         Fatigue.

·         Muscle weakness.

Conclusion:

This experiment serves as base to observe changes in humans associated with the removal of DNAse1L1.So,when DNAse1L1 is removed from mice it showed muscle weakness as major role is served by DNAse1L1 in muscle health.

Further function of DNAse1L1 is not clear. It degrades DNA so that it cannot enter cytosol.It protects mycocytes from DNA and when mycocytes are dead it removes DNA from them.DNAse1L1 also plays role in macrophages. Most of the function of DNAse1L1 is unknown so, there are chances of further research.