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Retinoic Acid Regulates Thymosin β Levels in Rat Neuroblastoma Cells
Author(s) -
Hall Alan K.,
Chen ShuCheng,
Hempstead James L.,
Morgan James I.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08173.x
Subject(s) - thymosin , retinoic acid , biology , endocrinology , medicine , receptor , cell culture , microbiology and biotechnology , biochemistry , genetics
A small acidic polypeptide, termed thymosin β10, has been identified and is present in the nervous system of the rat by the ninth day of gestation. Thymosin β10 levels rise during the remaining days of life in utero, and then decline to nearly undetectable values between the second and fourth week post partum. The present study investigates the possible developmental signals and mechanisms that might regulate the expression of thymosin β10 during neuroembryogenesis. Many cell lines derived from tumors of the central nervous system express thymosin β10, as well as its homologue gene product, thymosin β4. Because some of these cell lines respond to exogenously applied agents by increasing their apparent state of differentiation, we have determined whether thymosin β10 levels are coordinately modulated. In several neuroblastomas, including the B103 and B104 lines, retinoic acid elicits a time‐ and dose‐dependent increase in the content of thymosin β10, but not that of thymosin β4. The increase in thymosin β10 polypeptide is associated with a marked increase in the specific mRNA encoding this molecule. The mRNA for thymosin β4 is unaffected by retinoic acid. This is in contrast with the situation in vivo, where the expression of both genes decreases after birth. Other agents that influence the morphology of B104 cells, such as phorbol esters and dibutyryl cyclic AMP, have no influence on β‐thymosin levels. A range of steroids, which like retinoids act upon nuclear receptors, was also inactive. The stimulatory action of retinoic acid is detectable within 4 h, and thymosin β10 peptide levels continue to rise for at least 4 days. The influence of the isoprenoid is fully reversible and exhibits structural specificity. We believe that this culture system is mimicking the early rising phase of thymosin β10 levels in brain and that endogenous retinoids may be candidate physiological regulators of this gene.