Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.7)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 6, November-December, p. 1331–1336

doi: 10.17219/acem/32026

Publication type: review

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Thymosin β as an Actin-binding Protein with a Variety of Functions

Aleksandra Kuzan1,A,B,C,D,E,F

1 Department of Medical Biochemistry, Wroclaw Medical University, Poland

Abstract

According to current data, the thymosin β family is composed of 20 short (40–44 amino acid) peptides, but in a healthy human body only 2 are expressed – thymosin β4 and β10. Their most characteristic feature is the ability to form a complex with monomeric actin, thereby preventing polymerization into a filamentous form, hence the name Actin-Binding Protein (ABP). These peptides play numerous different functions. Among others, they affect the processes of carcinogenesis, differentiation and angiogenesis, influence metalloproteinase activity and accelerate wound healing. Moreover, significant biological activity has also been displayed by Tβ4 derived peptides: Ac-SDKP, the N-terminal fragment which is involved, inter alia, in stimulating angiogenesis and the inhibition of stem cell proliferation and Tβ4 sulfoxide, an oxidation product of one of the peptide methionine by hydrogen peroxide, which inhibit the development of inflammation. The properties of these peptides have potential applications in cardiovascular medicine, dermatology, ophthalmology and other medical areas.

Key words

thymosin β, Ac-SDKP, Tβ4 sulfoxide

References (41)

  1. Chen C, Li M, Yang H, Chai H, Fisher W, Yao Q: Roles of thymosins in cancers and other organ systems. World J Surg 2005, 29, 264–270.
  2. Sanders MC, Goldstein AL, Wang Y: Thymosin β4 (Fx Peptide) is a potent regulator of actin polymerization in living cells. PNAS 1992, 89, 4678–4682.
  3. Stoeva S, Hörger S, Voelter W: A novel β-thymosin from the sea urchin: extending the phylogenetic distribution of β thymosins from mammals to echinoderms. J Pept Sci 1997, 3, 282–290.
  4. Yang SP, Lee HJ, Su Y: Molecular cloning and structural characterization of the functional human thymosin β4 gene. Mol Cell Biochem 2005, 272, 97–105.
  5. Lere B, Massimo L, Bruce RZ: Thymosin β15 expression in tumor cell lines with varying metastatic potential. Clin Exp Metastasis 1998, 16, 227–233.
  6. Bao LR, Loda M, Janmey PA,Stewart R, Anandapte B, Zetter BR: Thymosin β15: A novel regulator of tumor cell motility upregulated in metastatic prostate cancer. Nat Med 1996, 2, 1322–1328.
  7. Smart N, Rossdeutsch A, Rile PR: Thymosin β4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis 2007, 10, 229–241.
  8. Carlier MF, Jean C, Rieger KJ, Lenfant M, Pantaloni D: Modulation of the interaction between Gactin and thymosin β4 by the ATP/ADP ratio: Possible implication in the regulation of actin dynamics. Proc Natl Acad Sci USA 1993, 90, 5034–5038.
  9. Carlier MF, Didry D, Erk I, Lepault J, Van Troys ML, Vandekerckhove J, Perelroizen I, Yin H, Doi Y, Pantaloni D: Thymosin β 4 is not a simple G-actin sequestering protein and interacts with F-actin at high concentration. J Biol Chem 1996, 271, 9231–9239.
  10. Bindschadler M, McGrath JL: Relationships between Actin Regulatory Mechanisms and Measurable State Variables. Annals of Biomedical Engineering 2007, 35, 995–1011.
  11. Sun HQ, Kwiatkowska K, Yin HL: β thymosins are not simple actin monomer buffering proteins. Insights from overexpression studies. J Biol Chem 1996, 271, 9223–9230.
  12. Lin, SC, Morrison-Bogorad M, Yin HL: Effects of thymosin β4 and thymosin β10 on actin structures in living cells. Cell Motil Cytoskeleton 1994, 27, 13–25.
  13. Golla R, Philp N, Safer D, Chintapalli J, Hoffman R, Collins L, Nachmias VT: Coordinate regulation of the cytoskeleton in 3T3 cells overexpressing thymosin β4. Cell Motil Cytoskeleton 1997, 38, 187–200.
  14. Hannappel E, Xu GJ, Morgan J, Hempstead J, Horecker BL: Thymosin β4: A ubiquitous peptide in rat and mouse tissues.Proc. Natl Acad Sci USA 1982, 79, 2172–2175.
  15. Huff T, Rosorius O, Otto AM, Muller CS, Ballweber E, Hannappel E, Mannherz HG: Nuclear localisation of the G-actin sequestering peptide thymosin beta 4. J Cell Sci 2004, 117, 5333–5341.
  16. Franco FJ, Diaz C, Barcia M, Arias P, Gomez-Marquez J, Soriano F, Mendez E, Freire M: Synthesis and apparent secretion of prothymosin alpha by different subpopulations of calf and rat thymocytes. Immunology 1989, 67, 263–268.
  17. Cavasin MA, Rhaleb NE, Yang XP, Carretero OA: Prolyl oligopeptidase is involved in release of the antifibrotic peptide Ac-SDKP. Hypertension 2004, 43, 1140–1145.
  18. Cingolani OH, Yang XP, Liu YH, Villanueva M, Rhaleb NE, Carretero OA: Reduction of cardiac fibrosis decreases systolic performance without affecting diastolic function in hypertensive rats. Hypertension 2004, 43, 1067–1073.
  19. Yang F, Yang XP, Liu YH, Xu J, Cingolani O, Rhaleb NE, Carretero OA: Ac-SDKP reverses inflammation and fibrosis in rats with heart failure after myocardial infarction. Hypertension 2004, 43, 229–236.
  20. Young JD, Lawrence AJ, MacLean AG, Leung BP, McInnes IB, Canas B, Pappin DJ, Stevenson RD: Thymosin β4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nat Med 1999, 5, 1424–1427.
  21. Huff T, Zerzawy D, Hannappel E: Interactions of β-thymosins, thymosin β4-sulfoxide, and N-terminally truncated thymosin β4 with actin studied by equilibrium centrifugation, chemical cross-linking and viscometry. Eur J Biochem 1995, 230, 650–657.
  22. Evans MA, Smart N, Dubé KN, Bollini S, Clark JE, Evans HG, Taams LS, Richardson R, Lévesque M, Martin P, Mills K, Riegler J, Price AN, Lythgoe MF, Riley PR: Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing. Nat Commun 2013, 4, 2081.
  23. Cha HJ, Jeong MJ, Kleinman HK: Role of thymosin beta 4 in tumor metastasis and angiogenesis. J Natl Cancer Inst 2003, 95, 1674–1680.
  24. Blain EJ, Mason DJ, Duance VC: The effect of thymosin beta 4 on articular cartilage chondrocyte matrix metalloproteinase expression. Biochem Soc Trans 2002, 30, 879–882.
  25. Philp D, Scheremeta B, Sibliss K, Zhou M, Fine EL, Nguyen M, Wahl L, Hoffman MP, Kleinman HK: Thymosin β4 promotes matrix metalloproteinase expression during wound repair. J Cell Physiol 2006, 208, 195–200.
  26. Rossdeutsch A, Smart N, Rile PR: Thymosin β4 and Ac-SDKP: Tools to mend a broken heart. J Mol Med 2007, 86, 29–35.
  27. Smart N, Risebro CA, Melville AAD, Moses K, Schwartz RJ, Chien KR, Riley PR: Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization. Nature 2007, 445, 177–182.
  28. Goldstein AL, Hannappel E, Sosne G, Kleinman HK: Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther 2012, 12, 37–51.
  29. Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D: Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 2004, 432, 466–472.
  30. Malinda KM, Sidhu GS, Mani H, Banaudha K, Maheshwari RK, Goldstein AL, Kleinman HK: Thymosin β4 accelerates wound healing. J Invest Dermatol 1999, 113, 364–368.
  31. Al-Nedawi KN, Czyz M, Bednarek R, Szemraj J, Swiatkowska M, Cierniewska-Cieslak A, Wyczolkowska J, Cierniewski CS: Thymosin β 4 induces the synthesis of plasminogen activator inhibitor 1 in cultured endothelial cells and increases its extracellular expression. Blood 2004, 103, 1319–1324.
  32. Sosne G, Hafeez S, Greenberry AL II, Kurpakus-Wheater M: Thymosin β4 promotes human conjunctival epithelial cell migration. Curr Eye Res 2002, 24, 268–273.
  33. Sosne G, Qiu P, Christopherson PL, Wheater MK: Thymosin β 4 suppression of corneal NFkappaB: A potential anti-inflammatory pathway. Exp Eye Res 2007, 84, 663–669.
  34. Sosne G, Siddiqi A, Kurpakus-Wheater M: Thymosin β4 inhibits corneal epithelial cell apoptosis after ethanol exposure in vitro. Invest Ophthalmol Vis Sci 2004, 45, 1095–1100.
  35. Leeanansaksiri W, DeSimone SK, Huff T, Hannappel E, Huff TF: Thymosin β 4 and its N-terminal tetrapeptide, AcSDKP, inhibit proliferation, and induce dysplastic, non-apoptotic nuclei and degranulation of mast cells. Chem Biodivers 2004, 1, 1091–1100.
  36. Goldstein AL: Thymosin β4: A new molecular target for antitumor strategies 67. JNCI 2003, 95, 1646–1647.
  37. Oh SY, Song JH, Gil JE, Kim JH, Yeom YI, Moon EY: ERK activation by Thymosin-beta-4 (Tβ4) overexpression induces paclitaxel-resistance. Exp Cell Res 2006, 312, 1651–1657.
  38. Koutrafouri V, Leoniadis L, Avgoustakis K, Livianou E, Czarnecki J, Ithakissios D, Evangelatos G: Effect of thymosin peptides on the chick chorioallantoic membrane angiogenesis model. Biochim Biophys Acta 2001, 1568, 60–66.
  39. Rossdeutsch A, Smart N, Dubé KN, Turner M, Riley PR: Essential role for thymosin β4 in regulating vascular smooth muscle cell development and vessel wall stability. Circ Res 2012, 111, 89–102.
  40. Shelton EL, Bader DM: Thymosin β4 mobilizes mesothelial cells for blood vessel repair. Ann N Y Acad Sci 2012, 1269, 125–130.
  41. Evans MA, Smart N, Dubé KN, Bollini S, Clark JE, Evans HG, Taams LS, Richardson R, Lévesque M, Martin P, Mills K, Riegler J, Price AN, Lythgoe MF, Riley PR: Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing. Nat Commun 2013, 4, 2081.
© Wroclaw Medical University