TB-500

Descrizione

Thymosin beta-4 is a protein that in humans is encoded by the TMSB4X gene.^[3]^[4]^[5] Recommended INN (International Nonproprietary Name) for thymosin beta-4 is ‘timbetasin’, as published by the World Health Organization (WHO). ^[6]

The protein consists (in humans) of 43 amino acids (sequence: SDKPDMAEI EKFDKSKLKK TETQEKNPLP SKETIEQEKQ AGES) and has a molecular weight of 4921 g/mol.^[7]

Thymosin-β₄ is a major cellular constituent in many tissues. Its intracellular concentration may reach as high as 0.5 mM.^[8] Following Thymosin α1, β₄ was the second of the biologically active peptides from Thymosin Fraction 5 to be completely sequenced and synthesized.^[9]

Tissue regeneration

Work with cell cultures and experiments with animals have shown that administration of thymosin β₄ can promote migration of cells, formation of blood vessels, maturation of stem cells, survival of various cell types and lowering of the production of pro-inflammatory cytokines. These multiple properties have provided the impetus for a worldwide series of on-going clinical trials of potential effectiveness of thymosin β₄ in promoting repair of wounds in skin, cornea and heart.^[17]

Such tissue-regenerating properties of thymosin β₄ may ultimately contribute to repair of human heart muscle damaged by heart disease and heart attack. In mice, administration of thymosin β₄ has been shown to stimulate formation of new heart muscle cells from otherwise inactive precursor cells present in the outer lining of adult hearts,^[18] to induce migration of these cells into heart muscle^[19] and recruit new blood vessels within the muscle.^[20]

Anti-inflammatory role for sulfoxide

In 1999 researchers in Glasgow University found that an oxidised derivative of thymosin β₄ (the sulfoxide, in which an oxygen atom is added to the methionine near the N-terminus) exerted several potentially anti-inflammatory effects on neutrophil leucocytes. It promoted their dispersion from a focus, inhibited their response to a small peptide (F-Met-Leu-Phe) which attracts them to sites of bacterial infection and lowered their adhesion to endothelial cells. (Adhesion to endothelial cells of blood vessel walls is pre-requisite for these cells to leave the bloodstream and invade infected tissue). A possible anti-inflammatory role for the β₄ sulfoxide was supported by the group’s finding that it counteracted artificially-induced inflammation in mice.

The group had first identified the thymosin sulfoxide as an active factor in culture fluid of cells responding to treatment with a steroid hormone, suggesting that its formation might form part of the mechanism by which steroids exert anti-inflammatory effects. Extracellular thymosin β₄ would be readily oxidised to the sulfoxide in vivo at sites of inflammation, by the respiratory burst.^[21]

REFERENCES:

GRCh38: Ensembl release 89: ENSG00000205542 – Ensembl, May 2017

^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.

^ Gómez-Márquez J, Dosil M, Segade F, Bustelo XR, Pichel JG, Dominguez F, Freire M (Oct 1989). “Thymosin-beta 4 gene. Preliminary characterization and expression in tissues, thymic cells, and lymphocytes”. Journal of Immunology. 143 (8): 2740–4. PMID 2677145.

^ Lahn BT, Page DC (Oct 1997). “Functional coherence of the human Y chromosome”. Science. 278(5338): 675–80. Bibcode:1997Sci…278..675L. doi:10.1126/science.278.5338.675. PMID 9381176.

^ Jump up to: ^a ^b “Entrez Gene: TMSB4X thymosin, beta 4, X-linked”.

^ “Lists of Recommended and Proposed INNs: List 80”. 2018.

^ “protein NP_066932”. NCBI.

^ Hannappel E (September 2007). “beta-Thymosins”. Annals of the New York Academy of Sciences. 1112 (1): 21–37. Bibcode:2007NYASA1112…21H. doi:10.1196/annals.1415.018. PMID 17468232.

^ Jump up to: ^a ^b Low TL, Hu SK, Goldstein AL (February 1981). “Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations”. Proceedings of the National Academy of Sciences of the United States of America. 78 (2): 1162–6. Bibcode:1981PNAS…78.1162L. doi:10.1073/pnas.78.2.1162. PMC 319967. PMID 6940133.

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Tissue regeneration

Anti-inflammatory role for sulfoxide

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