Thymosins, Lymphokines, and the Immunology of Aging

Zatz, Martin; Goldstein, Allan L.

doi:10.1159/000212709

Cited by 53 publications

(15 citation statements)

References 32 publications

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“…The a-prothymosin is an acidic nuclear protein containing 111 amino acids, which was first isolated from rat thymus (Haritos et al, 1994) and was thought to be associated with regulation of cellular immunity (Zatz and Goldstein, 1995). However, an accumulating body of evidence suggests that a-prothymosin is associated with cell proliferation, although the precise mechanism remains to be elucidated.…”

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confidence: 99%

Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma

Na²,

Mitry³

et al. 1997

Br J Cancer

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Summary Identification of gene products exclusively or abundantly expressed in cancer may yield novel tumour markers. We recently isolated a number of cDNA clones, including a-prothymosin, from rat hepatocellular carcinoma (HCC) using a subtraction-enhanced display technique. a-Prothymosin is involved in cell proliferation and is regulated by the oncogene c-myc in vitro. In the present study, we analysed a-prothymosin gene expression and its correlation with c-myc in patients with HCC, cirrhosis and adenoma and in normal controls. Hepatic aprothymosin messenger RNA (mRNA) levels were two-to 9.2-fold higher in tumoral tissues than in adjacent non-tumoral tissues in 14 of 17 patients with HCC, regardless of coexisting cirrhosis and viral hepatitis. No marked difference in a-prothymosin mRNA levels was present in patients with adenoma and hepatic cirrhosis and in healthy controls. The c-myc mRNA amounts were two-to fivefold increased in 11 of 17 patients with HCC and correlated significantly with those of a-prothymosin (P < 0.001). In situ hybridization revealed that increased aprothymosin mRNA was localized in the tumour nodules of the patients with HCC. These data suggest that overexpression of a-prothymosin in HCC patients, correlated with c-myc, is possibly involved in the tumorigenic process and may be a novel molecular marker for human HCC.

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confidence: 99%

Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma

Na²,

Mitry³

et al. 1997

Br J Cancer

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“…Thymosin a1 has been reported not only to be active in several assay systems for enhancement of immune function, both in vitro and in vivo, but also to be much more potent than the thymosin fraction 5 preparations from which it was isolated (for reviews, see refs. [3][4][5].…”

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confidence: 99%

Prothymosin alpha in human blood.

Panneerselvam¹,

Haritos²,

Caldarella³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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The major cross-reacting peptide in human plasma detected with a radioimmunoassay (RIA) for thymosin a, was identified as prothymosin a, based on its elution properties in gel-filtration chromatography and its amino acid composition after purification by HPLC. A small quantity (<10%) of the total cross-reacting material was recovered in fractions corresponding to lower molecular weight thymosin al-like peptides. The total quantity of cross-reacting material detected in human blood, expressed as thymosin a, equivalents, was 11-14 pmol/ml (-90% was recovered in the leukocyte fraction, =10% was in the plasma fraction, and 1-2% was in the erythrocyte fraction). The peptide present in leukocytes was also identified as prothymosin a. After correction for the 5-times lower molar reactivity of prothymosin a in the thymosin a, RIA employed in these experiments, we estimate that the content of prothymosin a in human blood is 55-70 pmol/ml (0.6-0.8 pg/ml). The relatively small quantities recovered in the erythrocyte and plasma fractions may be attributed to contamination of the former by leukocytes or to leakage from leukocytes into the plasma.Thymosin a1, an acidic peptide containing 28 amino acid residues (1), was first isolated from a calf thymus preparation called thymosin fraction 5, a biologically active mixture of peptides ranging in molecular weight from 1000 to 15,000 (2). Thymosin a1 has been reported not only to be active in several assay systems for enhancement of immune function, both in vitro and in vivo, but also to be much more potent than the thymosin fraction 5 preparations from which it was isolated (for reviews, see refs. 3-5).Radioimmunoassays (RIAs) for thymosin a1 have been developed in several laboratories (6)(7)(8)25) and employed for the analysis of cross-reacting material in serum or plasma (6, 9-12). Highest levels of immunoreactive peptides were found in cord plasma (6), but detectable quantities (0.6-3.7 ng of thymosin a1 equivalents per ml) were also present in the serum of adolescents (6) or normal adults (12). Of particular interest were reports that the levels of immunoreactive thymosin a,-like material were elevated in serum from patients with acquired immunodeficiency syndrome and also in a group of homosexual men (13,14). Another report, however, suggests that the high levels in serum from patients with acquired immunodeficiency syndrome may be due to the presence of a product of the gag gene of human immunodeficiency virus, which contains an amino acid sequence homologous to the sequence in thymosin a1 that was recognized by the antibody employed (15). This antiserum was also reported to block the replication of human immunodeficiency virus in permissive H9 cells (15).The identity and possible origin of the cross-reacting material in normal blood have not yet been established. A cross-reacting peptide purified from a preparation of Cohn fraction IV-1 by immunoaffinity chromatography was reported to resemble thymosin a1 in size and chromatographic properties (16). However, the i...

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“…Enhancement of helper and suppressor T cell activity was observed by thymosin al injection (Frasca et al 1985(Frasca et al , 1986(Frasca et al , 1987, and IL-2 production was increased by treatment with thymosin al, TF-5 and thymopentin (Zatz and Goldstein 1985;Frasca et al 1986;Meroni et al 1987). Stimulatory effect of TF-5 on colony-stimulating factor and interferon production was also reported (Zatz and Goldstein 1985). And treatment of thymosin al augmented antibody production in old mice as well as in young mice (Ershler et al 1985).…”

Section: Discussionmentioning

confidence: 88%

“…There are numerous studies of trying to restore decreased T cell functions in old mice with thymic hormones (Zatz and Goldstein 1985;Frasca et al 1985Frasca et al , 1986. In fact thymic hormones can restore cytokine production, such as interleukin-2 (IL-2), colony-stimulating factors, interferon etc., in the senescent mice (Zatz and Goldstein 1985;Frasca et al 1986 ;Meroni et al 1987).…”

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confidence: 99%