Cellular Levels of Thymosin Immunoreactive Peptides Are Linked to Proliferative Events: Evidence for a Nuclear Site of Action

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1990 May 1

PMID 2375791

Citations 20

Authors

C N Conteas

M G Mutchnick

K C Palmer

F E Weller

G D Luk

P H Naylor

M R Erdos

A L Goldstein

C Panneerselvam

B L HORECKER

Affiliations

Soon will be listed here.

Abstract

Thymosin alpha 1 (T alpha 1), the N-terminal 28-amino acid fragment of prothymosin alpha (ProT alpha), and ProT alpha, although originally isolated from whole thymus extracts, are also present in nonthymic cells and tissues. We used an ELISA with an antibody raised against T alpha 1 to investigate the relationship between intracellular levels of thymosin immunoreactive peptide(s) (TIP) and cell proliferation in a rat small intestinal IEC-6 cell line. Increasing TIP levels were observed during cell proliferation, which decreased when proliferation was halted by cellular contact inhibition. Serum feeding of cells previously rendered quiescent by serum starvation resulted in a significant increase in TIP within 1 hr. Conversely, serum starvation decreased TIP levels within 1 hr. Peak TIP levels appeared after 3 hr of serum incubation, while maximum [3H]thymidine incorporation was noted after 9 hr, suggesting maximum TIP concentrations in the G1 phase of the proliferative cycle. Immunoelectron microscopy demonstrated an association of TIP with condensed nuclear chromatin. These results support a relation of intracellular TIP levels to IEC-6 cell proliferation and also a nuclear site of action. HPLC analysis of cellular homogenates from proliferating IEC-6 cells revealed a peak of immune reactivity that elutes in the position of T alpha 1.

Citing Articles

Prothymosin α accelerates dengue virus-induced thrombocytopenia.

Yang M, Lin C, Chen Y, Lu I, Su B, Chen Y iScience. 2024; 27(1):108422.

PMID: 38213625 PMC: 10783621. DOI: 10.1016/j.isci.2023.108422.

Overexpression of prothymosin-α in glioma is associated with tumor aggressiveness and poor prognosis.

Kumar A, Kumar V, Arora M, Kumar M, Ammalli P, Thakur B Biosci Rep. 2022; 42(4).

PMID: 35297481 PMC: 9069441. DOI: 10.1042/BSR20212685.

Thymus-Pineal Gland Axis: Revisiting Its Role in Human Life and Ageing.

Rezzani R, Franco C, Hardeland R, Rodella L Int J Mol Sci. 2020; 21(22).

PMID: 33233845 PMC: 7699871. DOI: 10.3390/ijms21228806.

Prothymosin α variants isolated from CD8+ T cells and cervicovaginal fluid suppress HIV-1 replication through type I interferon induction.

Teixeira A, Yen B, Gusella G, Thomas A, Mullen M, Aberg J J Infect Dis. 2014; 211(9):1467-75.

PMID: 25404520 PMC: 4425839. DOI: 10.1093/infdis/jiu643.

Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages.

Mosoian A, Teixeira A, High A, Christian R, Hunt D, Shabanowitz J J Virol. 2006; 80(18):9200-6.

PMID: 16940531 PMC: 1563913. DOI: 10.1128/JVI.00589-06.

References

MCCLURE J, Lameris N, Wara D, Goldstein A . Immunochemical studies on thymosin: radioimmunoassay of thymosin alpha 1. J Immunol. 1982; 128(1):368-75. View

Hirokawa K, MCCLURE J, Goldstein A . Age-related changes in localization of thymosin in the human thymus. Thymus. 1982; 4(1):19-29. View

Haritos A, Goodall G, HORECKER B . Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc Natl Acad Sci U S A. 1984; 81(4):1008-11. PMC: 344752. DOI: 10.1073/pnas.81.4.1008. View

Haritos A, Tsolas O, HORECKER B . Distribution of prothymosin alpha in rat tissues. Proc Natl Acad Sci U S A. 1984; 81(5):1391-3. PMC: 344840. DOI: 10.1073/pnas.81.5.1391. View

Weller F, Mutchnick M, Keren D, Goldstein A, Naylor P . MicroELISA method for measurement of human serum thymosin alpha 1. J Immunol Methods. 1985; 80(1):45-53. DOI: 10.1016/0022-1759(85)90163-2. View

Goodall G, Dominguez F, HORECKER B . Molecular cloning of cDNA for human prothymosin alpha. Proc Natl Acad Sci U S A. 1986; 83(23):8926-8. PMC: 387046. DOI: 10.1073/pnas.83.23.8926. View

Eschenfeldt W, Berger S . The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA. Proc Natl Acad Sci U S A. 1986; 83(24):9403-7. PMC: 387146. DOI: 10.1073/pnas.83.24.9403. View

Conteas C, Majumdar A . The effects of gastrin, epidermal growth factor, and somatostatin on DNA synthesis in a small intestinal crypt cell line (IEC-6). Proc Soc Exp Biol Med. 1987; 184(3):307-11. DOI: 10.3181/00379727-184-42484. View

Kurokowa M, Lynch K, Podolsky D . Effects of growth factors on an intestinal epithelial cell line: transforming growth factor beta inhibits proliferation and stimulates differentiation. Biochem Biophys Res Commun. 1987; 142(3):775-82. DOI: 10.1016/0006-291x(87)91481-1. View

10.

Panneerselvam C, Haritos A, Caldarella J, HORECKER B . Prothymosin alpha in human blood. Proc Natl Acad Sci U S A. 1987; 84(13):4465-9. PMC: 305110. DOI: 10.1073/pnas.84.13.4465. View

11.

Gomez-Marquez J, Segade F . Prothymosin alpha is a nuclear protein. FEBS Lett. 1988; 226(2):217-9. DOI: 10.1016/0014-5793(88)81425-x. View

12.

Piltch A, Naylor P, Hayashi J . A cloned rat thymic epithelial cell line established from serum-free selective culture. In Vitro Cell Dev Biol. 1988; 24(4):289-93. DOI: 10.1007/BF02628829. View

13.

Watts J, Cary P, Crane-Robinson C . Prothymosin alpha is a nuclear protein. FEBS Lett. 1989; 245(1-2):17-20. DOI: 10.1016/0014-5793(89)80182-6. View

14.

Wada S, Naylor P, Naylor C, Goldstein A . Improved ELISA to measure thymosin alpha 1: comparison of whole and absorbed antisera. Int J Immunopharmacol. 1988; 10(7):795-801. DOI: 10.1016/0192-0561(88)90002-1. View

15.

Eschenfeldt W, Manrow R, Krug M, Berger S . Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products. J Biol Chem. 1989; 264(13):7546-55. View

16.

Gomez-Marquez J, Segade F, Dosil M, Pichel J, Bustelo X, Freire M . The expression of prothymosin alpha gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation. J Biol Chem. 1989; 264(15):8451-4. View

17.

Franco F, Diaz C, Barcia M, Arias P, Gomez-Marquez J, Soriano F . Synthesis and apparent secretion of prothymosin alpha by different subpopulations of calf and rat thymocytes. Immunology. 1989; 67(2):263-8. PMC: 1385268. View

18.

Makarova T, Grebenshikov N, Egorov C, Vartapetian A, Bogdanov A . Prothymosin alpha is an evolutionary conserved protein covalently linked to a small RNA. FEBS Lett. 1989; 257(2):247-50. DOI: 10.1016/0014-5793(89)81544-3. View

19.

McLean I, Nakane P . Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974; 22(12):1077-83. DOI: 10.1177/22.12.1077. View

20.

Goldstein A, Low T, McAdoo M, McClure J, Thurman G, Rossio J . Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977; 74(2):725-9. PMC: 392366. DOI: 10.1073/pnas.74.2.725. View