Hall A K, Chen S C, Hempstead J L, Morgan J I
Department of Neurosciences, Roche Institute of Molecular Biology, Nutley, New Jersey 07110-1199.
J Neurochem. 1991 Feb;56(2):462-8. doi: 10.1111/j.1471-4159.1991.tb08173.x.
A small acidic polypeptide, termed thymosin beta 10, has been identified and is present in the nervous system of the rat by the ninth day of gestation. Thymosin beta 10 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 beta 10 during neuroembryogenesis. Many cell lines derived from tumors of the central nervous system express thymosin beta 10, as well as its homologue gene product, thymosin beta 4. Because some of these cell lines respond to exogenously applied agents by increasing their apparent state of differentiation, we have determined whether thymosin beta 10 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 beta 10, but not that of thymosin beta 4. The increase in thymosin beta 10 polypeptide is associated with a marked increase in the specific mRNA encoding this molecule. The mRNA for thymosin beta 4 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 beta-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 beta 10 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 beta 10 levels in brain and that endogenous retinoids may be candidate physiological regulators of this gene.
一种名为胸腺素β10的小酸性多肽已被鉴定出来，在妊娠第九天时存在于大鼠的神经系统中。胸腺素β10水平在子宫内剩余的生命天数中上升，然后在产后第二至第四周下降到几乎检测不到的值。本研究调查了在神经胚胎发生过程中可能调节胸腺素β10表达的发育信号和机制。许多源自中枢神经系统肿瘤的细胞系表达胸腺素β10及其同源基因产物胸腺素β4。由于其中一些细胞系对外源施加的试剂有反应，通过增加其明显的分化状态，我们已经确定胸腺素β10水平是否受到协同调节。在几种神经母细胞瘤中，包括B103和B104细胞系，视黄酸引起胸腺素β10含量的时间和剂量依赖性增加，但不引起胸腺素β4的增加。胸腺素β10多肽的增加与编码该分子的特异性mRNA的显著增加相关。胸腺素β4的mRNA不受视黄酸影响。这与体内情况相反，在体内这两个基因的表达在出生后都会下降。其他影响B104细胞形态的试剂，如佛波酯和二丁酰环磷腺苷，对β-胸腺素水平没有影响。一系列与类视黄醇一样作用于核受体的类固醇也没有活性。视黄酸的刺激作用在4小时内即可检测到，胸腺素β10肽水平至少持续上升4天。类异戊二烯的影响是完全可逆的，并表现出结构特异性。我们认为这种培养系统模拟了大脑中胸腺素β10水平的早期上升阶段，内源性类视黄醇可能是该基因的候选生理调节因子。
