User:Victória Marcelle do Nascimento/caixa de areia 6117

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You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

Structure:

Endostatin is a polypeptide of 184 amino acids, corresponding to the globular domain 20kDa found in the C-Terminal COOH region of type 18 collagen

It is a globular protein that has two disulfide bonds: Cys162-302 and Cys264-294 and a zinc binding domain in its n-terminal, because of this it has a high affinity with growth factors and heparin. It can be generated by generated by proteolytic cleavage by proteases or metalloproteinases. After the proteolytic process, the endostatin generated may remain associated with the basal membrane (immobilized) or be released into the circulation (soluble endostatin). Since soluble and immobilized forms have different biological activities Another important factor to mention is that this protein has an alpha chain that has only one hydrogen atom in the side chain and thanks to this, it ends up being a small molecule and allows the enstilling of three of these polypeptides and the formation of homo and heterodincompounds, helping in their anti angiogenic functions. The structure was removed from the PDB by code 1KOE

Function:

As already said, endostatin has an anti angiogenic function and it was originally isolated as an angiogenesis inhibitor and proposed as an anti tumor therapeutic agent, being the most studied of endogenous angiogenesis inhibitors.

Relevance:

To portray a little more about it, I brought its relevance in relation to the population and scientific community from the point of view of the medical area by relating its functions with the treatment of two diseases: Hialoid Diseases and its progression which is Corneal Angiogenesis and the other tumor angiogenesis.

Hyaloid and Corneal Angiogenesis:

So the Hyaloid is the vitreous membrane of the cornea, it is a layer of collagen that separates the vitreous mood from the rest of the eye

And since Endostatin has been shown to be a product of collagen proteolytic neckline 18, even if its therapeutic potential has not yet been realized, the mutant collagen fragment 18, in which no endostatin production is possible, had a proven effect on hyaloid regression. This interesting discovery was made by the Olsen group, which indicated that collagen 18, and more specifically endostatin, promote vascular vessel regression, being consistent with the originally identified anti-angiogenic activity of endostatin. In addition, in the case of more severe cases such as corneal angiogenesis which is the resourcefulness of high vascularization, endostatin inhibits NV, which is the neovascularization of the cornea induced by BFGF (Basic Fibroblast Growth Factor), as well as vegf-induced vascular migration and proliferation (potent and multifunctional cytokine expressed in the vascular endothelium and which causes increased vascularity permeability and stimulates neovascularization). Local production of endostatin and neostatins -7 and -14 which are even smaller fragments of colagin 18 may occur during wound healing and they have potent anti-angiogenic and anti-lymphampangiogenic properties, but only endostatin is approved by the Food and Drug Administration (FDA) for the treatment of cancer-related NV.

Tumor Angiogenesis:

Now in Tumor Angiogenesis we have endostatin and tumstatin which are fragments of proteolytic neckline derived from collagen molecules. Despite their similarities, they share little sequential identity and can have independent roles.

Studies have shown that these compounds play an important role in the angiogenic response that accompanies thrombosis and tissue repair. The production of these endogenous angiogenesis inhibitors may help explain tumor numbness, first proposed by Folkman in 1971 where he states that if local angiogenic activity in a tumor is controlled by the balance of pro-angiogenic factors and angiogenesis inhibitors such as endostatin, it would take months or years to generate the appropriate genetic and physiological conditions necessary to balance and favor the active development of blood vessels and the growth of blood vessels and the growth of blood vessels tumor, leaving him in a state of numbness. Multiple genetic models in mice showed that tumors generated by transgenic expression of oncogenes and treated with endostatin initially remain small, with the proliferation of tumor cells largely offset by apoptosis. The synthesis of angiogenesis inhibitors by a primary tumor can also prevent distant metastases from progressing, since removal of a large primary tumor often correlates with the rapid growth of previously unidentified metastatic tumors in patients. Endostatin suppresses angiogenesis through many pathways that affect both cell viability and movement. In addition, it suppresses cell cycle control and anti-apoptosis genes in the proliferation of endothelial cells, resulting in cell death. Therefore, endostatin can prevent the activity of certain metalloproteins, since it can significantly affect 12% of the genes used by human endothelial cells.

Inquisitiveness:

An interesting observation is that although endostatin signaling can affect this large number of genes, its effects seem surprisingly limited. The reception of endostatin seems to affect only angiogenesis that arrives from pathogenic sources, such as tumors. Processes associated with angiogenesis, such as wound healing and reproduction, are apparently not affected by endostatin. This is because pathogenic derived angiogenesis usually involves signaling through integrated ones, which are directly affected by endostatin.

References: Browder, T.; Folkman, J.; Pirie-Shepherd, S. (2000). "O sistema hemostático como regulador da angiogênese"

Folkman, J. (1997). "Endostatina: um inibidor endógeno de angiogênese e crescimento tumoral"

Marneros, A.G.; Olsen, B.R. (2005). "Papel fisiológico do colágeno XVIII e endostatina". O Jornal FASEB

Nyberg, P.; Xie, L.; Kalluri, R. (2005). "Inibidores endógenos da angiogênese"

OReilly, EsM; Boehm, T.; Shing, Y.; Fukai, N.; Vasios, G.; Lane, W.W.; Flynn, E.; Birkhead, JR; Olsen, B.R.