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Ewald Hannappel - One of the best experts on this subject based on the ideXlab platform.
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high resolution mass spectrometry for Thymosins detection and characterization
Expert Opinion on Biological Therapy, 2015Co-Authors: Tiziana Cabras, Irene Messana, Federica Iavarone, Claudia Martelli, Daniela Delfino, Diana Valeria Rossetti, Ilaria Inserra, Barbara Manconi, Claudia Desiderio, Ewald HannappelAbstract:Objectives: The aim of this study was to characterize β and α Thymosins and their proteoforms in various tissues and bodily fluids by mass spectrometry and to look at their association with a wide variety of pathologies.Methods: A top–down proteomic platform based on high-performance liquid chromatography (HPLC) coupled to high-resolution LTQ-Orbitrap mass spectrometry (MS) was applied to the characterization of naturally occurring peptides.Results: In addition to thymosin β4 (Tβ4) and β10 (Tβ10), several post-translational modifications of both these peptides were identified not only in bodily fluids but also in normal and pathological tissues of different origins. The analysis of tissue specimens allowed the characterization of different C-terminal truncated forms of Tβ4 and Tβ10 together with other proteolytic fragments. The sulfoxide derivative of both Tβ4 and Tβ10 and the acetylated derivatives at lysine residues of Tβ4 were also characterized. Different proteoforms of prothymosin α, parathymosin α, ...
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Thymosin β4 and Tissue Transglutaminase. Molecular Characterization of Cyclic Thymosin β4
Protein Journal, 2013Co-Authors: Jana Knop, Thomas Huff, Heinrich Sticht, Ewald HannappelAbstract:Thymosin β4 is the prototype of β-Thymosins and is present in almost every mammalian cell. It is regarded to be the main intracellular G-actin sequestering peptide. Thymosin β4 serves as a specific glutaminyl substrate for guinea pig transglutaminase. In the absence of an appropriate additional aminyl donor an e-amino group of thymosin β4 serves also as an aminyl substrate and an intramolecular bond is formed concomitantly NH3 (17 Da) is lost. The molecular mass of the product is 4,949.6 Da. This is 16.3 Da less than the molecular mass of thymosin β4 (4,965.9 Da). Digestion with endopeptidases and Edman degradation of the fragments identified the exact position of the ring forming isopeptide bond. In spite of 3 glutaminyl and 9 lysyl residues of thymosin β4 only one isopeptide bond between Lys16 and Gln36 was formed (cyclic thymosin β4). These two amino acid residues are conserved in all β-Thymosins. Cyclic thymosin β4 still forms a complex with G-actin albeit the stability of the complex is about one fiftieth of the stability of the thymosin β4 × G-actin complex.
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Identification of interaction partners of β‐Thymosins: application of thymosin β4 labeled by transglutaminase
Annals of the New York Academy of Sciences, 2012Co-Authors: Jana Knop, Hans Georg Mannherz, Ewald HannappelAbstract:In this review, we identify potential interaction partners of the β-thymosin family. The proteins of this family are highly conserved peptides in mammals and yet only one intracellular (G-actin) and one cell-surface protein (β subunit of F1–F0 ATP synthase) were identified as interaction partners of thymosin β4. Cross-linking experiments may be a possible approach to discover additional proteins that interact with the β-thymosin family. It has previously been shown that thymosin β4 can be labeled at its glutaminyl residues with various cadaverines using tissue transglutaminase. Here, we illuminate recent results and give an outlook on upcoming work in the field.
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identification of interaction partners of β Thymosins application of thymosin β4 labeled by transglutaminase
Annals of the New York Academy of Sciences, 2012Co-Authors: Jana Knop, Hans Georg Mannherz, Ewald HannappelAbstract:In this review, we identify potential interaction partners of the β-thymosin family. The proteins of this family are highly conserved peptides in mammals and yet only one intracellular (G-actin) and one cell-surface protein (β subunit of F1–F0 ATP synthase) were identified as interaction partners of thymosin β4. Cross-linking experiments may be a possible approach to discover additional proteins that interact with the β-thymosin family. It has previously been shown that thymosin β4 can be labeled at its glutaminyl residues with various cadaverines using tissue transglutaminase. Here, we illuminate recent results and give an outlook on upcoming work in the field.
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Thymosin β4 and its posttranslational modifications
Annals of the New York Academy of Sciences, 2010Co-Authors: Ewald HannappelAbstract:Thymosin β 4 as well as the other members of the β-thymosin family are important G-actin sequestering peptides. The chemical properties, the biosynthesis, and posttranslational modifications (PTMs) of these peptides are discussed. During biosynthesis ofthymosin β 4 the initiator methionine is removed and the N-terminus is acetylated. Research on proteomics revealed several acetylated lysine residues and two phosphorylated threonine residues. The enormous number of phosphorylable and acetylable sites in the human proteome raises the question about the biological significance of these PTMs in the context of β-Thymosins. Presently, this question cannot be answered because neither the concentration of these modified β-Thymosins in cells is known nor the consequences of the modifications on the biological function(s) of β-Thymosins have been studied yet. Thymosin β 4 is also posttranslationally modified by transglutaminase forming covalent bonds with other molecules. Prolyl oligopeptidase generates ac-SDKP from thymosin β 4 . The concentration of C-terminal peptide fragments of thymosin β 4 is elevated in the blood of patients with rheumatoid arthritis.
Wolfgang Voelter - One of the best experts on this subject based on the ideXlab platform.
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the prognostic value of alpha Thymosins in breast cancer
Anticancer Research, 1998Co-Authors: Ourania E Tsitsilonis, Stanka Stoeva, E Bekris, Ioannis F Voutsas, Constantin N Baxevanis, Christos Markopoulos, S A Papadopoulou, Konstantinos Kontzoglou, J Gogas, Wolfgang VoelterAbstract:The prognosis of breast cancer is of major clinical importance and several histopathological biochemical and immunological variables have been reported to be useful prognostic factors. In the present study, we investigated the clinical significance of the levels of α-Thymosins in relation to established prognostic factors, both in breast cancer and nonmalignant breast lesions. α-thymosin levels were measured in breast tissue extracts by specific radioimmunoassays (RIAs) developed for human prothymosin α (ProTα) and parathymosin a (Para Tα) and were found to be significantly higher (up to 17,2-fold) in malignant but not in benign breast lesions, as compared to the values of the neighbouring tissues. When α-thymosin levels of the tumor samples were correlated with various known prognostic parameters a statistically significant correlation (p<0,05) was observed between the levels of ProTα in malignant tissues to the grade of cancer and the lymph node status of the patient. An association between ProTα levels with increase in risk of death from breast cancer was also noticed. These results suggest that the expression of α-Thymosins in human breast cancer a) depends on the proliferation status of the tumor, b) associates with established prognostic factors describing the metastatic potential of the tumor and c) is related to the overall survival of the patient. The fact that such relationships hold only for cancer tissues encourages the future use of α-Thymosins as potent prognostic factors in breast cancer.
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a novel β thymosin from the sea urchin extending the phylogenetic distribution of β Thymosins from mammals to echinoderms
Journal of Peptide Science, 1997Co-Authors: Stanka Stoeva, Susanne Horger, Wolfgang VoelterAbstract:The study of the phylogenetic distribution of the beta-thymosin family is important to elucidate its biological function further. A new thymosin, designated as thymosin beta 14, consisting of 40 amino acid residues and with a molecular weight of 4537 Da as determined by ion spray mass spectrometry, was isolated from the sea urchin. The N-terminus of this polypeptide is blocked by an acetyl group as found by matrix-assisted laser desorption mass spectrometric and amino acid analysis. The primary structure was elucidate by Edman degradation of the HPLC-purified thymosin beta 14 fragments produced by digestion with endoproteinase Asp-N and trypsin. Sequence comparison reveals that thymosin beta 14 is 73% homologous to thymosin beta 4, obtained from calf thymus. By isolating and characterising the structure of thymosin beta 14 from the sea urchin, an invertebrate, substantial knowledge about the phylogenetic distribution and evolution of beta-Thymosins is gained.
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A novel β‐thymosin from the sea urchin: extending the phylogenetic distribution of β‐Thymosins from mammals to echinoderms
Journal of Peptide Science, 1997Co-Authors: Stanka Stoeva, Susanne Horger, Wolfgang VoelterAbstract:The study of the phylogenetic distribution of the beta-thymosin family is important to elucidate its biological function further. A new thymosin, designated as thymosin beta 14, consisting of 40 amino acid residues and with a molecular weight of 4537 Da as determined by ion spray mass spectrometry, was isolated from the sea urchin. The N-terminus of this polypeptide is blocked by an acetyl group as found by matrix-assisted laser desorption mass spectrometric and amino acid analysis. The primary structure was elucidate by Edman degradation of the HPLC-purified thymosin beta 14 fragments produced by digestion with endoproteinase Asp-N and trypsin. Sequence comparison reveals that thymosin beta 14 is 73% homologous to thymosin beta 4, obtained from calf thymus. By isolating and characterising the structure of thymosin beta 14 from the sea urchin, an invertebrate, substantial knowledge about the phylogenetic distribution and evolution of beta-Thymosins is gained.
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expression of alpha Thymosins in human tissues in normal and abnormal growth
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: O.e. Tsitsiloni, P.p. Yialouris, Christos Markopoulos, J Gogas, J Stiakakis, A Koutselinis, S Bekris, D Panoussopoulos, V Kiortsis, Wolfgang VoelterAbstract:Radioimmunoassays specific for the N and C termini of human prothymosin alpha and the N terminus of human parathymosin alpha were employed for the measurement of the levels of alpha-Thymosins in human thymus, spleen, and liver during normal growth and intestine and breast in malignant growth. A differential expression of the two alpha-Thymosins was observed in thymus (prothymosin alpha-rich) and liver (parathymosin alpha-rich). A decline in the levels of both alpha-Thymosins was found with age, with prothymosin alpha in thymus showing the sharpest change (15- to 30-fold). The levels of both alpha-Thymosins were higher in malignant tissues as compared with healthy ones. In breast cancer, in particular, the mean increase for prothymosin alpha and parathymosin alpha was 17.9- and 11.5-fold, respectively. The major crossreactive material was characterized in all cases as intact prothymosin alpha and parathymosin alpha. These results suggest an in vivo relationship of the expression of alpha-Thymosins with the human tissue cell proliferation activity.
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The complete sequences of trout (Salmo gairdneri) thymosin β11 and its homologue thymosin β12
Biochemical Journal, 1992Co-Authors: P.p. Yialouris, B Coles, O.e. Tsitsiloni, B Schmid, Steven Howell, Alastair Aitken, Wolfgang Voelter, A. A. HaritosAbstract:Two forms of beta-Thymosins, designated thymosin beta 11 and thymosin beta 12, were isolated from trout (Salmo gairdneri) spleen. This suggests that the presence of two beta-Thymosins, previously thought to be a property of mammalian tissues only, is a more general phenomenon in vertebrate species. Both trout beta-Thymosins were found to be N-terminally blocked by a group identified as acetyl by m.s. Automated protein sequencing of tryptic, thermolytic and Staphylococcus aureus in 41-residue V8 proteinase fragments revealed that one of the two beta-Thymosins corresponds to the previously reported 41-residue-long sequence of thymosin beta 11 with two substitutions at positions 5 and 7, i.e. Asn instead of Asp, and Glu instead of Gln, whereas the other beta-thymosin, designated thymosin beta 12, was found to be a 42-residue polypeptide closely similar in sequence to thymosin beta 11, with five substitutions (i.e. at positions 5, 7, 10, 11 and 41, with Asp, Ala, Ser, Asn and Thr instead of Asn, Glu, Ala, Ser and Ser respectively) and one addition at position 42 (Ala). Comparison of the known six sequences of beta-Thymosins together with the sequences reported here showed that the sequence similarity of the two beta-Thymosins in trout (86%) is greater than that of the two beta-Thymosins in mammalian species (74%) and that residues at 28 positions are identical in all beta-Thymosins, the longer conserved segments located at positions 16-26 and 31-38.
Thomas Huff - One of the best experts on this subject based on the ideXlab platform.
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Thymosin β4 and Tissue Transglutaminase. Molecular Characterization of Cyclic Thymosin β4
Protein Journal, 2013Co-Authors: Jana Knop, Thomas Huff, Heinrich Sticht, Ewald HannappelAbstract:Thymosin β4 is the prototype of β-Thymosins and is present in almost every mammalian cell. It is regarded to be the main intracellular G-actin sequestering peptide. Thymosin β4 serves as a specific glutaminyl substrate for guinea pig transglutaminase. In the absence of an appropriate additional aminyl donor an e-amino group of thymosin β4 serves also as an aminyl substrate and an intramolecular bond is formed concomitantly NH3 (17 Da) is lost. The molecular mass of the product is 4,949.6 Da. This is 16.3 Da less than the molecular mass of thymosin β4 (4,965.9 Da). Digestion with endopeptidases and Edman degradation of the fragments identified the exact position of the ring forming isopeptide bond. In spite of 3 glutaminyl and 9 lysyl residues of thymosin β4 only one isopeptide bond between Lys16 and Gln36 was formed (cyclic thymosin β4). These two amino acid residues are conserved in all β-Thymosins. Cyclic thymosin β4 still forms a complex with G-actin albeit the stability of the complex is about one fiftieth of the stability of the thymosin β4 × G-actin complex.
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Thymosin β4 Is Not Always the Main β‐Thymosin in Mammalian Platelets
Annals of the New York Academy of Sciences, 2007Co-Authors: Thomas Huff, Christian S G Muller, Ewald HannappelAbstract:p-Thymosins constitute a family of highly conserved 5-kDa polypeptides. Thymosin β 4 , the most abundant member of this family, is expressed in most mammalian cell types and is regarded as the main intracellular G-actin sequestering peptide. In addition to this important intracellular function several other activities have been attributed to this peptide. Thymosin β 4 is released from human platelets and cross-linked to fibrin after activation of platelets with thrombin. While in most mammalian tissues thymosin β 4 is accompanied by a second member of this peptide family, in human platelets only thymosin p4 is present. To elucidate if it is common to mammalian platelets that only one β-thymosin is present, we analyzed platelets from several mammals for their p-thymosin content. In human platelets only thymosin β 4 could be detected, whereas in bovine platelets thymosin β 9 , which is normally the minor p-thymosin in bovine tissues, was identified as the main β-thymosin. In rabbit platelets, thymosin β 4 is not simply replaced by the most homologous thymosin β 4 Ala , as might be expected from sequence homology. Thymosin β 4 Ala and thymosin β 10 were found, but thymosin β 10 is present in about 2.5-fold higher amounts. Because thymosin β 4 Ala possesses about threefold higher affinity to G-actin, compared to thymosin β 4 , β 10 , and β 9 , we suggest that expression of p-Thymosins is triggered by functional requirements and not sequence homology.
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intracellular β Thymosins
2007Co-Authors: Ewald Hannappel, Thomas Huff, Daniel SaferAbstract:The β-Thymosins are a family of highly conserved polar peptides consisting of 40 to 44 amino acid residues. All β-Thymosins bind monomeric G-actin in a 1:1 complex. The dissociation constant of the complex is in the micromolar range and allows for fast binding and release of G-actin. Because of the high intracellular concentration of β-Thymosins (up to 500 µM) in most vertebrate cells, β-Thymosins are considered the main intracellular G-actin sequestering peptides. Thymosin β4 binds to G-actin in an extended conformation, and folds into a stable conformation upon binding. The N- and C-termini of thymosin β4 contact the barbed and pointed ends of the monomeric actin. Thymosin β4 is present in the nucleus as well as the cytoplasm and might be responsible for sequestering nuclear actin. Even minor cell damage might be responsible for the release of β-Thymosins detectable in the extracellular fluids. Extracellular β-Thymosins affect matrix metallo-proteinases, chemotaxis, angiogenesis and wound healing. However, only very little is known about the molecular mechanisms mediating the effects attributed to extracellular β-Thymosins.
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the Thymosins prothymosin α parathymosin and β Thymosins structure and function
Vitamins and Hormones Series, 2003Co-Authors: Ewald Hannappel, Thomas HuffAbstract:Abstract The studies on Thymosins were initiated in 1965, when the group of A. White searched for thymic factors responsible for the physiological functions of thymus. To restore thymic functions in thymic-deprived or immunodeprived animals, as well as in humans with primary immunodeficiency diseases and in immunosuppressed patients, a standardized extract from bovine thymus gland called thymosin fraction 5 was prepared. Thymosin fraction 5 indeed improved immune response. It turned out that thymosin fraction 5 consists of a mixture of small polypeptides. Later on, several of these peptides (polypeptide β 1 , thymosin α 1 , prothymosin α, parathymosin, and thymosin β 4 ) were isolated and tested for their biological activity. The research of many groups has indicated that none of the isolated peptides is really a thymic hormone; nevertheless, they are biologically important peptides with diverse intracellular and extracellular functions. Studies on these functions are still in progress. The current status of knowledge of structure and functions of the Thymosins is discussed in this review. © 2003, Elsevier Science (USA).
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chemotherapeutic drugs change actin skeleton organization and the expression of β Thymosins in human breast cancer cells
Journal of Cancer Research and Clinical Oncology, 2002Co-Authors: Angela M Otto, Thomas Huff, Christian S G Muller, Ewald HannappelAbstract:Purpose: Elevated expression of the β-thymosin isotypes Tβ4, Tβ10, and T15 appears to be involved in the manifestation of a malignant phenotype of human tumor cells, including those of mammary carcinomas. This has evoked an interest in these peptides as diagnostic/prognostic tumor markers. If increased levels of β-Thymosins correspond to tumor malignancy, the question arises whether tumor growth inhibition induced by chemotherapeutic drugs would reduce their expression. Methods: Two human breast cancer cell lines, the estrogen receptor(ER)-positive MCF-7 and the ER-negative MDA-MB231, were thus analyzed for the amount of β-thymosin mRNAs by RNase protection assay and for the respective peptide levels by HPLC following different hormonal and drug treatments. Results: Both cell lines, growing in medium with 10% FCS, contain Tβ4 (400–500 fg/cell) and Tβ10 (about 100 fg/cell), but no Tβ15. Incubating MCF-7 cells with tamoxifen (1 µM) for 5 days resulted in about 80% growth inhibition and in reduction of intracellular Tβ4 and Tβ10 concentrations by about 40%. Levels of Tβ4 and Tβ10-mRNA were reduced by about 60%. In contrast, cisplatin (2 µM) changed neither the peptide concentrations nor the mRNA levels of β-Thymosins, in spite of marked growth inhibition. In addition, no changes in β-thymosin expression were observed in MDA-MB231 cells treated with either drug. MCF-7 cells maintained in estrogen-poor medium (10% horse serum) or stimulated to grow with estradiol (1 nM) had Tβ4 and Tβ10 concentrations reduced by about 30%, but changes in Tβ4- and Tβ10-mRNA levels did not correspond to those of the peptide. Conclusion: Expression of Tβ4 and Tβ10 mRNAs and their peptides is differentially regulated and does not correlate with growth. Instead, reduced β-thymosin expression may be linked to more intensive TRITC-phalloidin staining of F-actin lining the membrane at sites of intimate cell-cell contacts, while increased β-thymosin levels appear in cells with more extensive substrate adhesion. This suggests that β-Thymosins play a role in cell surface dynamics.
A. A. Haritos - One of the best experts on this subject based on the ideXlab platform.
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The complete sequences of trout (Salmo gairdneri) thymosin β11 and its homologue thymosin β12
Biochemical Journal, 1992Co-Authors: P.p. Yialouris, B Coles, O.e. Tsitsiloni, B Schmid, Steven Howell, Alastair Aitken, Wolfgang Voelter, A. A. HaritosAbstract:Two forms of beta-Thymosins, designated thymosin beta 11 and thymosin beta 12, were isolated from trout (Salmo gairdneri) spleen. This suggests that the presence of two beta-Thymosins, previously thought to be a property of mammalian tissues only, is a more general phenomenon in vertebrate species. Both trout beta-Thymosins were found to be N-terminally blocked by a group identified as acetyl by m.s. Automated protein sequencing of tryptic, thermolytic and Staphylococcus aureus in 41-residue V8 proteinase fragments revealed that one of the two beta-Thymosins corresponds to the previously reported 41-residue-long sequence of thymosin beta 11 with two substitutions at positions 5 and 7, i.e. Asn instead of Asp, and Glu instead of Gln, whereas the other beta-thymosin, designated thymosin beta 12, was found to be a 42-residue polypeptide closely similar in sequence to thymosin beta 11, with five substitutions (i.e. at positions 5, 7, 10, 11 and 41, with Asp, Ala, Ser, Asn and Thr instead of Asn, Glu, Ala, Ser and Ser respectively) and one addition at position 42 (Ala). Comparison of the known six sequences of beta-Thymosins together with the sequences reported here showed that the sequence similarity of the two beta-Thymosins in trout (86%) is greater than that of the two beta-Thymosins in mammalian species (74%) and that residues at 28 positions are identical in all beta-Thymosins, the longer conserved segments located at positions 16-26 and 31-38.
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The complete sequences of trout (Salmo gairdneri) thymosin beta 11 and its homologue thymosin beta 12.
The Biochemical journal, 1992Co-Authors: P.p. Yialouris, B Coles, O.e. Tsitsiloni, B Schmid, Steven Howell, Alastair Aitken, Wolfgang Voelter, A. A. HaritosAbstract:Two forms of beta-Thymosins, designated thymosin beta 11 and thymosin beta 12, were isolated from trout (Salmo gairdneri) spleen. This suggests that the presence of two beta-Thymosins, previously thought to be a property of mammalian tissues only, is a more general phenomenon in vertebrate species. Both trout beta-Thymosins were found to be N-terminally blocked by a group identified as acetyl by m.s. Automated protein sequencing of tryptic, thermolytic and Staphylococcus aureus in 41-residue V8 proteinase fragments revealed that one of the two beta-Thymosins corresponds to the previously reported 41-residue-long sequence of thymosin beta 11 with two substitutions at positions 5 and 7, i.e. Asn instead of Asp, and Glu instead of Gln, whereas the other beta-thymosin, designated thymosin beta 12, was found to be a 42-residue polypeptide closely similar in sequence to thymosin beta 11, with five substitutions (i.e. at positions 5, 7, 10, 11 and 41, with Asp, Ala, Ser, Asn and Thr instead of Asn, Glu, Ala, Ser and Ser respectively) and one addition at position 42 (Ala). Comparison of the known six sequences of beta-Thymosins together with the sequences reported here showed that the sequence similarity of the two beta-Thymosins in trout (86%) is greater than that of the two beta-Thymosins in mammalian species (74%) and that residues at 28 positions are identical in all beta-Thymosins, the longer conserved segments located at positions 16-26 and 31-38.
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evidence for the extranuclear localization of Thymosins in thymus
Cellular and Molecular Life Sciences, 1992Co-Authors: O.e. Tsitsiloni, P.p. Yialouris, Wolfgang Voelter, H Echner, A. A. HaritosAbstract:A new radioimmunoassay has been developed for thymosin β4 by generating rabbit polyclonal antibodies against the synthetic N-terminal peptide fragment 1–15 coupled to KLH. The synthetic analogue [Tyr12]-thymosin β4 (1–15) was used as tracer. This radioimmunoassay, with a useful range of 10–1000 pmoles, showed cross-reactivity with the second homologous β-thymosin of man and rat (thymosin β10) but not of calf (thymosin β9). This radioimmunoassay, together with an improved radioimmunoassay for the N-terminus of parathymosin α, was employed for the measurement of the levels of thymosin β4 and parathymosin α in nuclear and extranuclear extracts of calf thymus. The bulk of these polypeptides was found in the extranuclear material whereas only traces were observed in the nuclear environment, which indicates the extranuclear localisation of α- and β-Thymosins.
O.e. Tsitsiloni - One of the best experts on this subject based on the ideXlab platform.
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expression of alpha Thymosins in human tissues in normal and abnormal growth
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: O.e. Tsitsiloni, P.p. Yialouris, Christos Markopoulos, J Gogas, J Stiakakis, A Koutselinis, S Bekris, D Panoussopoulos, V Kiortsis, Wolfgang VoelterAbstract:Radioimmunoassays specific for the N and C termini of human prothymosin alpha and the N terminus of human parathymosin alpha were employed for the measurement of the levels of alpha-Thymosins in human thymus, spleen, and liver during normal growth and intestine and breast in malignant growth. A differential expression of the two alpha-Thymosins was observed in thymus (prothymosin alpha-rich) and liver (parathymosin alpha-rich). A decline in the levels of both alpha-Thymosins was found with age, with prothymosin alpha in thymus showing the sharpest change (15- to 30-fold). The levels of both alpha-Thymosins were higher in malignant tissues as compared with healthy ones. In breast cancer, in particular, the mean increase for prothymosin alpha and parathymosin alpha was 17.9- and 11.5-fold, respectively. The major crossreactive material was characterized in all cases as intact prothymosin alpha and parathymosin alpha. These results suggest an in vivo relationship of the expression of alpha-Thymosins with the human tissue cell proliferation activity.
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The complete sequences of trout (Salmo gairdneri) thymosin β11 and its homologue thymosin β12
Biochemical Journal, 1992Co-Authors: P.p. Yialouris, B Coles, O.e. Tsitsiloni, B Schmid, Steven Howell, Alastair Aitken, Wolfgang Voelter, A. A. HaritosAbstract:Two forms of beta-Thymosins, designated thymosin beta 11 and thymosin beta 12, were isolated from trout (Salmo gairdneri) spleen. This suggests that the presence of two beta-Thymosins, previously thought to be a property of mammalian tissues only, is a more general phenomenon in vertebrate species. Both trout beta-Thymosins were found to be N-terminally blocked by a group identified as acetyl by m.s. Automated protein sequencing of tryptic, thermolytic and Staphylococcus aureus in 41-residue V8 proteinase fragments revealed that one of the two beta-Thymosins corresponds to the previously reported 41-residue-long sequence of thymosin beta 11 with two substitutions at positions 5 and 7, i.e. Asn instead of Asp, and Glu instead of Gln, whereas the other beta-thymosin, designated thymosin beta 12, was found to be a 42-residue polypeptide closely similar in sequence to thymosin beta 11, with five substitutions (i.e. at positions 5, 7, 10, 11 and 41, with Asp, Ala, Ser, Asn and Thr instead of Asn, Glu, Ala, Ser and Ser respectively) and one addition at position 42 (Ala). Comparison of the known six sequences of beta-Thymosins together with the sequences reported here showed that the sequence similarity of the two beta-Thymosins in trout (86%) is greater than that of the two beta-Thymosins in mammalian species (74%) and that residues at 28 positions are identical in all beta-Thymosins, the longer conserved segments located at positions 16-26 and 31-38.
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The complete sequences of trout (Salmo gairdneri) thymosin beta 11 and its homologue thymosin beta 12.
The Biochemical journal, 1992Co-Authors: P.p. Yialouris, B Coles, O.e. Tsitsiloni, B Schmid, Steven Howell, Alastair Aitken, Wolfgang Voelter, A. A. HaritosAbstract:Two forms of beta-Thymosins, designated thymosin beta 11 and thymosin beta 12, were isolated from trout (Salmo gairdneri) spleen. This suggests that the presence of two beta-Thymosins, previously thought to be a property of mammalian tissues only, is a more general phenomenon in vertebrate species. Both trout beta-Thymosins were found to be N-terminally blocked by a group identified as acetyl by m.s. Automated protein sequencing of tryptic, thermolytic and Staphylococcus aureus in 41-residue V8 proteinase fragments revealed that one of the two beta-Thymosins corresponds to the previously reported 41-residue-long sequence of thymosin beta 11 with two substitutions at positions 5 and 7, i.e. Asn instead of Asp, and Glu instead of Gln, whereas the other beta-thymosin, designated thymosin beta 12, was found to be a 42-residue polypeptide closely similar in sequence to thymosin beta 11, with five substitutions (i.e. at positions 5, 7, 10, 11 and 41, with Asp, Ala, Ser, Asn and Thr instead of Asn, Glu, Ala, Ser and Ser respectively) and one addition at position 42 (Ala). Comparison of the known six sequences of beta-Thymosins together with the sequences reported here showed that the sequence similarity of the two beta-Thymosins in trout (86%) is greater than that of the two beta-Thymosins in mammalian species (74%) and that residues at 28 positions are identical in all beta-Thymosins, the longer conserved segments located at positions 16-26 and 31-38.
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evidence for the extranuclear localization of Thymosins in thymus
Cellular and Molecular Life Sciences, 1992Co-Authors: O.e. Tsitsiloni, P.p. Yialouris, Wolfgang Voelter, H Echner, A. A. HaritosAbstract:A new radioimmunoassay has been developed for thymosin β4 by generating rabbit polyclonal antibodies against the synthetic N-terminal peptide fragment 1–15 coupled to KLH. The synthetic analogue [Tyr12]-thymosin β4 (1–15) was used as tracer. This radioimmunoassay, with a useful range of 10–1000 pmoles, showed cross-reactivity with the second homologous β-thymosin of man and rat (thymosin β10) but not of calf (thymosin β9). This radioimmunoassay, together with an improved radioimmunoassay for the N-terminus of parathymosin α, was employed for the measurement of the levels of thymosin β4 and parathymosin α in nuclear and extranuclear extracts of calf thymus. The bulk of these polypeptides was found in the extranuclear material whereas only traces were observed in the nuclear environment, which indicates the extranuclear localisation of α- and β-Thymosins.