What are Beta Thymosins
Beta-thymosins (β-thymosins) are a family of highly conserved polar 5 kDa peptides. This peptide family was originally thought to be thymic hormones. However, in the last decade the thymosin β4 peptides, as well as other members of this ubiquitous peptide family, were identified as the main intracellular G-actin sequestering peptides. E. Hannappel, in a review article in 2007 reported that large amounts of thymosin β4 were found in many cells. Even though scientists postulated a general biological function for beta-thymosins, identifying such a function proved tedious. Finally, after much work, in 1990, Dan Safer and his colleagues recognized that thymosin β4 sequesters G-actin. Beta-thymosins are now known to be the main intracellular G-actin-sequestering peptides in most vertebrate cells. Thymosin β4 was found to be unstructured but folds into a stable conformation after binding to G-actin. The peptide is present in the nucleus as well as in the cytoplasm and may be responsible for sequestering nuclear actin. Additionally, it was found that thymosin peptides are present in high concentrations in almost every cell. Also, since β-thymosins bind monomeric actin in a 1:1 complex they can act as actin buffers. The interaction of β-thymosins with actin monomers prevents the polymerization of monomeric actin into actin filaments but supplies a pool of actin monomers when the cell needs filaments. Changes in the expression of these peptides appear to be related to cell differentiation. It is thought that increased expression of β-thymosins or the synthesis of a β-thymosin which is normally not expressed, may promote metastasis possibly by increasing the cells mobility. Thymosin β4 can be detected outside of cells in blood plasma or in wound fluids. Multiple recent studies have uncovered several important functions for thymosin β₄ which are related to the regeneration of injured tissues including skin and heart tissues. In addition, β-thymosins and their fragments have been reported to exhibit biological effects such as the induction of metallo-proteinases, chemotaxis, angiogenesis and inhibition of inflammation as well as the inhibition of bone marrow stem cell proliferation. Thymosin β₄ has been reported to promote endothelial cell migration via the activation of Akt2 kinase at the leading edge of the cell. During skeletal muscle injury, increased levels of thymosin β₄ are produced by muscle fibers and surrounding immune cells. Furthermore, thymosin β₄ is known to chemoattract satellite cell-derived myoblasts and myocytes involved in skeletal muscle regeneration. In addition, thymosin β₄ has been reported to interact physically with F₁-F₀ ATP synthase on the plasma membrane to increase the local concentration of ATP. This interaction stimulates the P2X₄ purinergic receptor to elicit a migratory response from endothelial cells. As such, thymosin β₄ appears to be an important chemotactic factor involved in stem/progenitor cell-mediated tissue regeneration.
More recently, the functional peptide Ac-SDKP, an anti-inflammatory thymosin β4 peptide, has been used for tissue engineering for the creation of polymeric implants useful for soft tissue regeneration. The reason is that the thymosin β4-derived anti-inflammatory Ac-SDKP peptides have been identified to decrease macrophage infiltration and transforming growth factor beta (TGF-β) expression. TGF-β controls proliferation, cellular differentiation, and other cellular functions. Normally, these experiments employ scaffolds filled with a mixture of collagen and selected peptides. The peptides are loaded in porous scaffolds through collagen gel embedding, so that peptides can be released in a controlled fashion. This allows mimicking the degradation of the extracellular matrix.
Reference
Goldstein AL.; History of the discovery of the thymosins. Ann N Y Acad Sci. 2007 Sep;1112:1-13. Epub 2007 Jun 28.
Hannappel E.; beta-Thymosins. Ann N Y Acad Sci. 2007 Sep;1112:21-37. Epub 2007 Apr 27.
Hara T.; Thymosins and muscle regeneration. Vitamines and Hormones 2011;87:277-90. doi: 10.1016/B978-0-12-386015-6.00032-9.
Thomas Huff, Christian S.G. Mueller, Angela M. Otto, Roland Netzker, Ewald Hannappel; Beta-Thymosins, small acidic peptides with multiple functions. The International Journal of Biochemistry & Cell Biology 33 (2001) 205–220.
Angela L. Zachman, Spencer W. Crowder, Ophir Ortiz, Katarzyna J. Zienkiewicz, Christine M. Bronikowski, Shann S. Yu, MS, Todd D. Giorgio, Scott A. Guelcher, Joachim Kohn, and Hak-Joon Sung; Pro-angiogenic and Anti-inflammatory Regulation by Functional Peptides Loaded in Polymeric Implants for Soft Tissue Regeneration. TISSUE ENGINEERING: Part A Volume 19, Numbers 3 and 4, 2013.
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06/13/2014