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验证单细胞模型系统中的表观遗传遗传:激素印迹的多代效应。

Verification of epigenetic inheritance in a unicellular model system: multigenerational effects of hormonal imprinting.

机构信息

Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.

出版信息

Cell Biol Int. 2012 Oct 1;36(10):951-9. doi: 10.1042/CBI20110677.

Abstract

The unicellular Tetrahymena has receptors for hormones of higher vertebrates, produces these hormones, and their signal pathways are similar. The first encounter with a hormone in higher dose provokes the phenomenon of hormonal imprinting, by which the reaction of the cell is quantitatively modified. This modification is transmitted to the progeny generations. The duration of the single imprinter effect of two representative signal molecules, insulin and 5-HT (5-hydroxytryptamine), in two concentrations (10(-6) and 10(-15) M) were studied. The effects of imprinting were followed in 5 physiological indices: (i) insulin binding, (ii) 5-HT synthesis, (iii) swimming behaviour, (iv) cell growth and (v) chemotaxis in progeny generations 500 and 1000. The result of each index was different from the non-imprinted control functions, growth rate, swimming behaviour and chemotactic activity to insulin being enhanced, while others, e.g. synthesis and chemotactic responsiveness of 5-HT and the binding of insulin were reduced. This means that a function-specific heritable epigenetic change during imprinting occurs, and generally a single encounter with a femtomolar hormone concentration is enough for provoking durable and heritable imprinting in Tetrahymena. The experiments demonstrate the possibility of epigenetic effects at a unicellular level and call attention to the possibility that the character of unicellular organisms has changed through to the present day due to an enormous amount of non-physiological imprinter substances in their environment. The results - together with results obtained earlier in mammals - point to the validity of epigenetic imprinting effects throughout the animal world.

摘要

单细胞四膜虫具有高等脊椎动物激素的受体,能产生这些激素,其信号通路也相似。首次遇到高剂量的激素会引发激素印迹现象,从而使细胞的反应在数量上发生改变。这种改变会传递给后代。我们研究了两种代表性信号分子胰岛素和 5-HT(5-羟色胺)在两种浓度(10(-6) 和 10(-15) M)下的单一印迹效应持续时间。在 500 和 1000 代后代中,我们研究了印迹的 5 种生理指标的影响:(i)胰岛素结合,(ii)5-HT 合成,(iii)游动行为,(iv)细胞生长和(v)趋化性。每个指标的结果都与未印迹的对照功能不同,对胰岛素的生长率、游动行为和趋化性活性增强,而其他指标,如 5-HT 的合成和趋化性反应性以及胰岛素的结合则降低。这意味着在印迹过程中发生了功能特异性的可遗传表观遗传变化,并且通常单次遇到皮摩尔激素浓度足以在四膜虫中引发持久的可遗传印迹。实验证明了在单细胞水平上存在表观遗传效应的可能性,并提醒人们,由于其环境中存在大量非生理印迹物质,单细胞生物的特征可能已经发生了变化。这些结果——与早期在哺乳动物中获得的结果一起——指向了整个动物界表观遗传印迹效应的有效性。

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