The effects of KTS disintegrins on endothelial cells. Meghan Catherine Brown

ISBN: 9780549772026

Published:

NOOKstudy eTextbook

131 pages


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The effects of KTS disintegrins on endothelial cells.  by  Meghan Catherine Brown

The effects of KTS disintegrins on endothelial cells. by Meghan Catherine Brown
| NOOKstudy eTextbook | PDF, EPUB, FB2, DjVu, talking book, mp3, ZIP | 131 pages | ISBN: 9780549772026 | 4.73 Mb

Integrins play an important role in cell adhesion, migration, signaling, differentiation, cycle progression and survival and is also involved in multiply steps in the angiogenic process. The integrin alpha1beta1 is an essential adhesion receptor thatMoreIntegrins play an important role in cell adhesion, migration, signaling, differentiation, cycle progression and survival and is also involved in multiply steps in the angiogenic process. The integrin alpha1beta1 is an essential adhesion receptor that is required to bind cells to the extracellular matrix protein collagen type IV.

Disintegrins are the largest family of anti-adhesive molecules found in viper snake venom, which are either monomeric or dimeric. There are different motifs that have been discovered such as RDG and MLD, and these disintegrins can bind to different integrins. Obtustatin and viperastatin are the two shortest known disintegrins containing 41 amino acids and have an integrin-binding loop containing a KTS motif.

Each of these disintegrins binds exclusively and inhibits the adhesion of alpha1beta1 integrin to collagen IV. The active motifs of these two disintegrins were determined by producing recombinant proteins and mutating the active site to determine the KTS motif, where threonine was the most essential amino acid within the tri-peptide motif.-The effects of obtustatin were examined on endothelial cells. Obtustatin is able to bind and endocytosis into endothelial cells. Also, there is an SH3 domain binding motif located in the C-terminus of obtustatin and is able to interact with cellular proteins.

The process of angiogenesis is a multiple step pathway and obtustatin has been shown to be a potent inhibitor of three key steps within this pathway: proliferation, migration and lumen formation. Obtustatin is able to decreases endothelial cells proliferation by inducing apoptosis via an extrinsic mechanism, as well as, inhibit growth factor induced migration and vessel-like structure formation in vitro in endothelial cells.

Two in vivo angiogenesis models were used- the Japanese quail egg and mouse model obtustatin was able to inhibit angiogenesis in the presence of growth factors.-Obtustatin is a potent inhibitor of angiogenesis and is able to inhibit endothelial cells in three key steps of this process. The studies may contribute to developing a new generation of angiostatic drugs, as well as increasing general knowledge in the cell biology field.



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