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Ewald Hannappel - One of the best experts on this subject based on the ideXlab platform.
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Thymosin Fraction 5 re evaluated after 35 years by high resolution mass spectrometry
Expert Opinion on Biological Therapy, 2018Co-Authors: Ewald Hannappel, Federica Iavarone, Massimo CastagnolaAbstract:Objectives: We reevaluated a lyophilized sample of Thymosin Fraction 5, stored for 37 years at room temperature, by high-resolution mass spectrometry in terms of stability and yet uncharacterized p...
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Thymosin Fraction 5 re-evaluated after 35 years by high-resolution mass spectrometry
2018Co-Authors: Ewald Hannappel, Federica Iavarone, Massimo CastagnolaAbstract:Objectives: We reevaluated a lyophilized sample of Thymosin Fraction 5, stored for 37 years at room temperature, by high-resolution mass spectrometry in terms of stability and yet uncharacterized polypeptides that could be biological important substances. 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 molecular characterization of polypeptides present in Thymosin Fraction 5. Results: We detected more than 100 monoisotopic masses corresponding to Thymosin β4 and truncated forms of ubiquitin, proThymosin α, Thymosin β4, and Thymosin β9. Additionally, we discovered a new polypeptide present in Thymosin Fraction 5 and identified it as intact SH3 domain-binding glutamic acid-rich-like protein 3. Conclusion: In spite of the well-known proteolytic processes inherent to the preparation of Thymosin Fraction 5, still uncharacterized polypeptides as well as truncated forms of already well-known Thymosins are present in Fraction 5 after long-term storage. Therefore, continuing characterization of Thymosin Fraction 5 is even nowadays highly promising.
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the β Thymosins intracellular and extracellular activities of a versatile actin binding protein family
Cytoskeleton, 2009Co-Authors: Hans Georg Mannherz, Ewald HannappelAbstract:The β-Thymosins are N-terminally acetylated peptides of about 5 kDa molecular mass and composed of about 40–44 amino acid residues. The first member of the family, Thymosin β4, was initially isolated from Thymosin Fraction 5, prepared in five steps from calf thymus. Thymosin β4 was supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. Various paracrine effects have indeed been reported for these peptides such as cardiac protection, angiogenesis, stimulation of wound healing, and hair growth. Besides these paracrine effects, it was noted that β-Thymosins occur in high concentration in the cytoplasm of many eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it became apparent from in vitro experiments that they preferentially bind to monomeric (G-)actin and stabilize it in its monomeric form. Due to this ability the β-Thymosins are the main intracellular actin sequestering factor, i.e., they posses the ability to remove monomeric actin from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur in activated cells. In this review we will concentrate on the intracellular activity and localization of the β-Thymosins, i.e., their modulating effect on the actin cytoskeleton. Cell Motil. Cytoskeleton, 2009. © 2009 Wiley-Liss, Inc.
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the β Thymosins intracellular and extracellular activities of a versatile actin binding protein family
Cytoskeleton, 2009Co-Authors: Hans Georg Mannherz, Ewald HannappelAbstract:The beta-Thymosins are N-terminally acetylated peptides of about 5 kDa molecular mass and composed of about 40-44 amino acid residues. The first member of the family, Thymosin beta4, was initially isolated from Thymosin Fraction 5, prepared in five steps from calf thymus. Thymosin beta4 was supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. Various paracrine effects have indeed been reported for these peptides such as cardiac protection, angiogenesis, stimulation of wound healing, and hair growth. Besides these paracrine effects, it was noted that beta-Thymosins occur in high concentration in the cytoplasm of many eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it became apparent from in vitro experiments that they preferentially bind to monomeric (G-)actin and stabilize it in its monomeric form. Due to this ability the beta-Thymosins are the main intracellular actin sequestering factor, i.e., they posses the ability to remove monomeric actin from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur in activated cells. In this review we will concentrate on the intracellular activity and localization of the beta-Thymosins, i.e., their modulating effect on the actin cytoskeleton.
Allan L. Goldstein - One of the best experts on this subject based on the ideXlab platform.
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complete amino acid sequence of bovine Thymosin f34 a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations differentiation of thymus dependent lymphocyte dna nucleotidylexotransferase acetylserine nh2 te
2016Co-Authors: Allan L. GoldsteinAbstract:The amino acid sequence of Thymosin 134, a poly- peptide isolated from calf thymus, was determined. Thymosin (34 is composed of 43 amino acid residues and has a molecular weight of 4982 and an isoelectric point of 5.1. The NH2 terminus of the peptide is blocked by an acetyl group. This molecule induces expression of terminal deoxynucleotidyl transferase (DNA nu- cleotidylexotransferase, EC 2.7.7.31) in transferase-negative mu- rine thymocytes in vivo and in vitro. Thus, it appears that Thymosin ,34 acts on lymphoid stem cells and may control the early stages of the maturation process of thymus-dependent lymphocytes. This peptide is one of several present in Thymosin Fraction 5 that par- ticipates in the regulation, differentiation, and function of thy- mus-dependent thymocytes.
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history of the discovery of the Thymosins
Annals of the New York Academy of Sciences, 2007Co-Authors: Allan L. GoldsteinAbstract:From a historical perspective, the studies that led to the isolation and characterization of the Thymosins began in earnest in the early 1960s in the laboratory of Abraham White at the Albert Einstein College of Medicine in New York. In a 1966 paper in the Proceedings of the National Academy of Sciences, U.S., we first named these thymic-derived factors "Thymosins." By 1972, the Thymosin team had moved to the University of Texas Medical Branch in Galveston (UTMB) where an extremely talented group of young scientists and students succeeded over the next 6 years in preparing and testing a highly active partially purified calf thymus preparation, termed Thymosin Fraction-5 (TF5), which was amenable for scale-up and suitable for clinical use. In 1974, we received the first IND for a thymic hormone preparation from the FDA to begin a phase-I study with TF5 in children with primary immunodeficiency diseases at the University of California Medical Center in San Francisco. The immunorestorative and potentially life-saving properties of TF5 in clinical medicine were first documented in a landmark paper in 1975 by Drs. Arthur Ammann and Diane Wara in the New England Journal of Medicine. TF5 consists of a family of at least 40 mostly small acidic polypeptides, with molecular weights ranging from 1000 to 15,000 Da. This article will identify the key scientists and the milestones involved in the initial studies with TF5 that have led to the chemical characterization of the Thymosins and to translational studies from the lab bench to the clinic.
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Thymosin Fraction 5 inhibits the proliferation of the rat neuroendocrine mmq pituitary adenoma and c6 glioma cell lines in vitro
Endocrinology, 1998Co-Authors: Bryan L. Spangelo, Allan L. Goldstein, Derald D Farrimond, Mahesh M Thapa, Charles M Bulathsinghala, Kay Lynn Bowman, Alaleh Sareh, Francis M Hughes, Mahnaz BadamchianAbstract:Cytokines such as interleukin-1 (IL-1) and IL-6 stimulate the hypothalamic-pituitary-adrenal (HPA) axis. In addition, these proteins affect pituitary cell proliferation in vitro. Thymosin Fraction 5 (TF5) is a partially purified preparation of the bovine thymus that enhances immune system functioning. Because TF5 similarly stimulates the HPA axis, we examined the effects of this preparation on neuroendocrine tumor cell proliferation. Cells of the PRL-secreting rat anterior pituitary adenoma, MMQ (5–50 × 103 cells/well), were exposed to vehicle (RPMI-1640 containing 2.5% FCS, 7.5% horse serum, and antibiotics) or TF5 (100–500 μg/ml) for up to 96 h and the proliferation of MMQ cells monitored using the MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide). TF5-mediated inhibition of cell proliferation was dependent on both TF5 concentration and the initial MMQ cell number. Minimal reductions in optical densities resulted from exposure to 100 μg/ml TF5, whereas the highest concentration ...
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complete amino acid sequence analysis of a peptide isolated from the thymus that enhances release of growth hormone and prolactin
Endocrinology, 1991Co-Authors: Mahnaz Badamchian, Bryan L. Spangelo, Robert M Macleod, Tania Damavandy, Allan L. GoldsteinAbstract:We have previously reported that Thymosin Fraction 5 (TF5), a partially purified calf thymus preparation, contains a peptide(s) that can enhance the production of GH and/or PRL from rat anterior pituitary cells in vitro. Using reverse phase HPLG, we have now isolated and chemically characterized from TF5 a peptide possessing this activity. This peptide, termed MB-35, is a highly charged basic molecule of 35 amino acid residues and a mol wt of 3756. A computer-assisted search of published protein sequences has revealed that this peptide has a 100% homology with a region of the histone H2A. Biological studies using rat pituitary cells have revealed that MB-35 is active alone or in combination with GH-releasing factor (GRF) or TRH and can increase the production of GH and/or PRL beyond that achievable with GH-releasing factor and TRH alone. The observation that histone H2A, the parent molecule, is without activity is of keen interest, since it suggests that nucleoproteins may have heretofore unknown physiolo...
Mahnaz Badamchian - One of the best experts on this subject based on the ideXlab platform.
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Thymosin Fraction 5 possesses antiproliferative properties in hl 60 human promyelocytic leukemia cells characterization of an active peptide
Annals of the New York Academy of Sciences, 2007Co-Authors: Bryan L. Spangelo, Joseph D Roach, Freidun Hadi, Ali A Damavandy, Jordan L Plieskatt, Mahnaz BadamchianAbstract:Thymosin Fraction-5 (TF5) is a protein preparation of the bovine thymus. TF5 stimulates many assays of T cell-mediated immunity. We found that TF5 substantially suppressed proliferation of the rat C6 glioma and MMQ pituitary adenoma cell lines. Our current research using the promyelocytic cell line HL-60 suggests that TF5 also prevents proliferation of human myeloid leukemia cells. Our objective is the purification and chemical characterization of TF5 peptide components responsible for inhibition of HL-60 proliferative capacity. Using the inhibition of HL-60 cell proliferation, we have chemically characterized TF5 using fast protein liquid chromatography (FPLC), reversed-phase high-performance liquid chromatography (RP-HPLC), and high-performance capillary electrophoresis (HPCE). Vital dye-exclusion, oxidative metabolism of chromogenic dyes, and clonogenic growth profiles were used to determine rates of HL-60 proliferation. Our results identified an approximately 6000 Da component of TF5 capable of inducing HL-60 growth arrest. Synchronized HL-60 cells exposed to TF5 and its various constituents were subjected to cytometric analysis by flow cytometry. TF5-treated HL-60 cells had an increased subdiploid faction (i.e., sub-G1) compared to control cells. TF5 also increased Annexin V staining in randomly cycling HL-60 cells. Thus, a TF5 subFraction possesses growth-suppressive activity for human myeloid neoplasms. Our results indicate that this effect is characterized by at least one hallmark of apoptosis. Future clinical management strategies for certain leukemias may involve the use of thymic peptides.
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presence of a peptide component of Thymosin Fraction 5 manifesting discrete cytostatic properties in hl 60 human promyelocytic leukemia cells
International Immunopharmacology, 2005Co-Authors: Bryan L. Spangelo, Mahnaz Badamchian, Derald D Farrimond, Melissa Pompilius, Nicole Stevens, Ria Nieva, Sachin Shroff, Charlene R Johnson, David W JarvisAbstract:Thymosin Fraction-5 (TF5), an array of small molecular weight peptides present in crude extracts of the adult bovine thymus, contains numerous constituents with demonstrable biological activity. Because TF5 generally enhances immune reactivity in a variety of settings, and additionally restricts proliferation of certain neoplasms, we examined the effects of TF5 on proliferative capacity in the human promyelocytic leukemia cell line HL-60. Vital dye-exclusion, oxidative metabolism of chromogenic dyes, and clonogenic growth profiles were monitored to assess rates of cellular proliferation; our results demonstrate that TF5 restricted HL-60 cell growth, an influence that exhibited comparable potency and efficacy among all three indices. This antiproliferative activity was labile, insofar as medium conditioned in HL-60 cells for 24 h became devoid of the initial growth-suppressive activity after 24-h culture when subsequently administered to naive cultures. Review of cytoarchitectural traits, chromatin staining by TUNEL, and fluorescent cytometric analyses demonstrated that TF5 failed to elicit apoptosis, however, suggesting that this material instead drove treated cells into growth arrest and an unanticipated cytostasis. Qualitatively similar responses were noted in the human monoblastic leukemia cell line U937. Partial purification of TF5 by FPLC yielded a component containing an antiproliferative activity associated with the ∼1000-Da Fraction. These results demonstrate that TF5 contains a sub-Fraction possessing a growth-suppressive activity capable of restraining normal proliferation of human myeloid neoplasms via the apparent induction of true cytostasis.
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Thymosins chemistry and biological properties in health and disease
Expert Opinion on Biological Therapy, 2004Co-Authors: Mahnaz BadamchianAbstract:This paper will review the historical background that has generated our present interest in the actions of the Thymosins in biological therapy. It will also discuss the multiple actions of the Thymosins in the immune, endocrine and central nervous systems. The isolation from the thymus gland of the Thymosins, a family of biologically active molecules with hormone-like properties, was first described in 1966 by AL Goldstein and A White. Since that time, significant progress has been made in understanding the role of the Thymosins in immunity and the nature of the growth factors, cytokines and chemokines they modulate. The Thymosins include a family of biochemically and functionally distinct polypeptides with clinically important physiological properties. In the early 1970s, preclinical studies establishing the immunorestorative effects of a partially purified Thymosin preparation termed Thymosin Fraction 5 (TF5) provided the scientific foundation for the first clinical trials with TF5 in 1974. TF5 was effe...
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Thymosin Fraction 5 inhibits the proliferation of the rat neuroendocrine mmq pituitary adenoma and c6 glioma cell lines in vitro
Endocrinology, 1998Co-Authors: Bryan L. Spangelo, Allan L. Goldstein, Derald D Farrimond, Mahesh M Thapa, Charles M Bulathsinghala, Kay Lynn Bowman, Alaleh Sareh, Francis M Hughes, Mahnaz BadamchianAbstract:Cytokines such as interleukin-1 (IL-1) and IL-6 stimulate the hypothalamic-pituitary-adrenal (HPA) axis. In addition, these proteins affect pituitary cell proliferation in vitro. Thymosin Fraction 5 (TF5) is a partially purified preparation of the bovine thymus that enhances immune system functioning. Because TF5 similarly stimulates the HPA axis, we examined the effects of this preparation on neuroendocrine tumor cell proliferation. Cells of the PRL-secreting rat anterior pituitary adenoma, MMQ (5–50 × 103 cells/well), were exposed to vehicle (RPMI-1640 containing 2.5% FCS, 7.5% horse serum, and antibiotics) or TF5 (100–500 μg/ml) for up to 96 h and the proliferation of MMQ cells monitored using the MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide). TF5-mediated inhibition of cell proliferation was dependent on both TF5 concentration and the initial MMQ cell number. Minimal reductions in optical densities resulted from exposure to 100 μg/ml TF5, whereas the highest concentration ...
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complete amino acid sequence analysis of a peptide isolated from the thymus that enhances release of growth hormone and prolactin
Endocrinology, 1991Co-Authors: Mahnaz Badamchian, Bryan L. Spangelo, Robert M Macleod, Tania Damavandy, Allan L. GoldsteinAbstract:We have previously reported that Thymosin Fraction 5 (TF5), a partially purified calf thymus preparation, contains a peptide(s) that can enhance the production of GH and/or PRL from rat anterior pituitary cells in vitro. Using reverse phase HPLG, we have now isolated and chemically characterized from TF5 a peptide possessing this activity. This peptide, termed MB-35, is a highly charged basic molecule of 35 amino acid residues and a mol wt of 3756. A computer-assisted search of published protein sequences has revealed that this peptide has a 100% homology with a region of the histone H2A. Biological studies using rat pituitary cells have revealed that MB-35 is active alone or in combination with GH-releasing factor (GRF) or TRH and can increase the production of GH and/or PRL beyond that achievable with GH-releasing factor and TRH alone. The observation that histone H2A, the parent molecule, is without activity is of keen interest, since it suggests that nucleoproteins may have heretofore unknown physiolo...
T Kishimoto - One of the best experts on this subject based on the ideXlab platform.
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thymus lymphocytes in uraemic rats and the effect of Thymosin Fraction 5 in vitro
Clinical and Experimental Immunology, 2008Co-Authors: Shinichi Ikemoto, T Kishimoto, Seiji Wada, Nobuyuki Hayahara, M MaekawaAbstract:Cellular immunity of thymus lymphocytes in uraemic rats was studied. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the response of thymus lymphocytes to concanavalin A (Con A) significantly decreased in severely uraemic rats, but did not change in moderately uraemic rats. However, when the thymus lymphocytes were pretreated with Thymosin Fraction 5, the response to Con A was ameliorated in severely uraemic rats. There was a significant correlation between the effect of Thymosin Fraction 5 on Con A response and Con A response of thymus lymphocytes. In addition, serum from severe uraemic rats suppressed the response of normal thymus lymphocytes to Con A. These results indicate that severe uraemia may cause an impairment in maturation of thymus lymphocytes, which can be improved by Thymosin Fraction 5 in vitro.
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protective effect of Thymosin Fraction 5 in animals with experimentally induced uremia
Clinical and Experimental Nephrology, 2000Co-Authors: Shinichi Ikemoto, Seiji Wada, Kazunobu Sugimura, Masato Kamizuru, Ryoji Yasumoto, Keisuke Yamamoto, T KishimotoAbstract:Background. Growth factors such as insulin-like growth factor, epidermal growth factor, and hepatocyte growth factor have been reported to be effective in the treatment of acute renal failure, but their effectiveness in chronic renal failure has not been reported. Thymosin, a glycoprotein extract obtained from calf thymus, is also known to have growth factor-like activity. In this study, we investigated the protective effect of Thymosin Fraction 5 (TF5), isolated from Thymosin, in mice and rats with experimentally induced uremia. Methods. Uremia was induced in mice by administering cis-Diammine-dichloroplatinum CDDP; 5 mg/kg, intraperitoneally once a week for 5 weeks. From the start of CDDP administration, mice in groups 1, 2 and 3, respectively, were given subcutaneous injections of saline or 1 mg/kg or 3 mg/kg of TF5 three times a week for 5 weeks. Uremia was induced in rats using the 5/6 renal ablation model. Rats in groups 1 and 2, respectively, were given subcutaneous injections of saline or 3 mg/kg of TF5 three times a week from the fifth to the twelfth week after removal of the right kidney, for a total of 8 weeks. Results. In uremic mice, 6 weeks after the start of CDDP administration, serum urea nitrogen (SUN) levels were 40.1 ± 16.4, 20.6 ± 6.6, and 20.2 ± 5.3 mg/dl in groups 1, 2, and 3, respectively, and the level was significantly lower in groups 2 and 3 than in group 1 (P < 0.05). In the uremic rats, 13 weeks after the removal of the right kidney, SUN levels were 105.2 ± 20.1 and 82.9 ± 11.6 mg/dl in groups 1 and 2, respectively, and serum creatinine levels were 2.22 ± 0.89 and 1.56 ± 1.06 mg/dl in groups 1 and 2, respectively, with a significant difference in both SUN and serum creatinine between groups 1 and 2 (P < 0.05). Conclusion. These results suggest the possibility that TF5 has a protective effect against progression of uremia.
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augmentation of antitumor activity of 5 deoxy 5 fluorouridine by Thymosin Fraction 5 in mouse bladder cancer cells in vitro and in vivo
Cancer Letters, 1999Co-Authors: Shinichi Ikemoto, Seiji Wada, Kazunobu Sugimura, Keisuke Yamamoto, R Yasumoto, T KishimotoAbstract:Abstract 5′-Deoxy-5-fluorouridine (5′-dFUrd) is a prodrug of 5-fluorouracil (5-FUra) activated by pyrimidine nucleoside phosphorylase (PyN Pase), mainly by uridine phosphorylase (Urd Pase) in rodents and by thymidine phosphorylase (TdR Pase) in humans, which is preferentially located in tumor tissues compared to normal tissues. It has been reported that PyN Pase is induced by cytokines such as tumor necrosis factor (TNF), interleukin-1α (IL-1α) and interferon (IFN). Thymosin is a glycoprotein extract obtained from the calf thymus and is a potent immunopotentiating preparation. In this study, the antiproliferative activity of 5′-dFUrd used in combination with Thymosin Fraction 5 (TF5) was investigated in mouse bladder cancer cell line MBT-2 in vitro and in vivo. In vitro TF5 enhanced the activity of 5′-dFUrd by up to 4.11-fold, whereas the activity of other cytostatics such as 5-FUra, mitomycin C, adriamycin, cis -platinum, etoposide, vinblastine and methrotrexate was not changed. In vivo when the effects of combination therapy with 5′-dFUrd and TF5 in C3H/HeN mice implanted with MBT2 were studied, tumor growth was not suppressed by TF5 alone while tumor growth was suppressed to some degree by 5′-dFUrd alone. However, tumor growth suppression was enhanced when 5′-dFUrd was used in combination with TF5. In order to investigate this mechanism, Urd Pase in MB2 was measured, and it was found that TF5 increased enzyme activity by up to 1.8-fold in MBT2. This increased susceptibility might be a result of the induction of Urd Pase, which is the essential enzyme for the conversion of 5′-dFUrd to 5-FUra. These results suggested that the therapeutic benefit of 5′-dFUrd would be improved by its use in combination with TF5 and the modulation of converting enzymes for antitumor prodrugs could be a novel therapeutic strategy for treating human cancers.
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Thymosin Fraction 5 does not influence urinary tract carcinogenesis by phenacetin and n butyl n 4 hydroxybutyl nitrosamine in non shi mice
Oncology Research, 1995Co-Authors: Takashi Murai, T Kishimoto, Seiji Wada, Y Kinoshita, F Hato, S Kimura, Satoru Mori, H Iwata, Susumu Makino, Tadao OoharaAbstract:The effect of Thymosin Fraction 5 (TF5) on the promotion and progression phases of urinary tract carcinogenesis induced by consecutive administration of phenacetin and N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in NON/Shi mice was investigated. The study was carried out twice with a minor modification to the protocol in the second experiment. Fifty-seven male NON/Shi mice in experiment 1 and 100 mice in experiment 2 were each divided into four groups. Phenacetin was administered for 8 weeks in experiment 1 and 12 weeks in experiment 2, and subsequently BBN was given for 6 weeks in both cases, for total observation periods of 30 and 34 weeks, respectively. Sixty micrograms of TF5 per mouse was inoculated subcutaneously twice a week during (group 2) or after (group 3) BBN exposure, or both periods (group 4). Group 1 served as a control group without TF5 treatment. Histopathological examination revealed no effects on either induction of urinary tract carcinomas or distant metastasis from renal pelvic carcinomas in either experiment.
Hans Georg Mannherz - One of the best experts on this subject based on the ideXlab platform.
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the β Thymosins intracellular and extracellular activities of a versatile actin binding protein family
Cytoskeleton, 2009Co-Authors: Hans Georg Mannherz, Ewald HannappelAbstract:The β-Thymosins are N-terminally acetylated peptides of about 5 kDa molecular mass and composed of about 40–44 amino acid residues. The first member of the family, Thymosin β4, was initially isolated from Thymosin Fraction 5, prepared in five steps from calf thymus. Thymosin β4 was supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. Various paracrine effects have indeed been reported for these peptides such as cardiac protection, angiogenesis, stimulation of wound healing, and hair growth. Besides these paracrine effects, it was noted that β-Thymosins occur in high concentration in the cytoplasm of many eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it became apparent from in vitro experiments that they preferentially bind to monomeric (G-)actin and stabilize it in its monomeric form. Due to this ability the β-Thymosins are the main intracellular actin sequestering factor, i.e., they posses the ability to remove monomeric actin from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur in activated cells. In this review we will concentrate on the intracellular activity and localization of the β-Thymosins, i.e., their modulating effect on the actin cytoskeleton. Cell Motil. Cytoskeleton, 2009. © 2009 Wiley-Liss, Inc.
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the β Thymosins intracellular and extracellular activities of a versatile actin binding protein family
Cytoskeleton, 2009Co-Authors: Hans Georg Mannherz, Ewald HannappelAbstract:The beta-Thymosins are N-terminally acetylated peptides of about 5 kDa molecular mass and composed of about 40-44 amino acid residues. The first member of the family, Thymosin beta4, was initially isolated from Thymosin Fraction 5, prepared in five steps from calf thymus. Thymosin beta4 was supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. Various paracrine effects have indeed been reported for these peptides such as cardiac protection, angiogenesis, stimulation of wound healing, and hair growth. Besides these paracrine effects, it was noted that beta-Thymosins occur in high concentration in the cytoplasm of many eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it became apparent from in vitro experiments that they preferentially bind to monomeric (G-)actin and stabilize it in its monomeric form. Due to this ability the beta-Thymosins are the main intracellular actin sequestering factor, i.e., they posses the ability to remove monomeric actin from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur in activated cells. In this review we will concentrate on the intracellular activity and localization of the beta-Thymosins, i.e., their modulating effect on the actin cytoskeleton.