【作者】 郭进军；

【导师】 黄爱龙；

【作者基本信息】 重庆医科大学 ， 内科学， 2006， 博士

【摘要】 细胞在高渗环境下首先通过细胞外离子迅速内流和细胞内水外流来保证细胞内外的渗透压平衡,此时伴有细胞皱缩等形态改变,这是细胞对高渗应激的即刻反应,但它的代偿保护作用是暂时和有限的,并且细胞内持续的高离子状态对细胞是非常有害的,可以诱发细胞凋亡或死亡。此时细胞会激活另外一个长效代偿机制,那就是通过增加一系列渗透压反应基因的转录翻译,从而增加有机渗透物合成、促进胞外有机渗透物内流或减少有机渗透物降解,最终使有机渗透物在细胞内聚集,从而恢复细胞内外的渗透压平衡,这些有机渗透物对细胞是无害的。目前的研究表明渗透压反应基因的转录合成增加是依赖于特异性转录因子TonEBP与TonE增强子元件的结合而启动的。真核细胞的DNA在细胞核内是以染色质的形式存在的。DNA缠绕组蛋白组成核小体,然后进一步形成染色质,组蛋白对DNA来说既是一个结构上的保护因素又是一个功能上的抑制因素。基因转录作为一个以DNA为模板的酶学过程必然要涉及到局部染色质如何打开以利于转录起始的过程,这就是染色质重塑过程。目前发现的染色质重塑事件主要有两种,一种是组蛋白翻译后共价修饰,另外是一种ATP酶依赖的核小体重塑。TonEBP作为高渗应激信号途径的一个核转录因子,它启动靶基因转录更多还原

【Abstract】 Eukaryotic cell membrane is permeable to water. When a cell experiences hypertonic stress, water is withdrawn from the cell along the osmotic gradient and Na+, Cl-, and K+ ions are accumulated within the cell, which results in cell shrinkage. This condition is detrimental because high ionic strength destabilizes proteins and compromises cellular functions. Cells respond to this situation by replacing these ions with organic osmolytes, which is able to resume osmotic equilibrium and preserve cell volume without perturbing macromolecular structure and function. A series of experiments have demonstrated that extracellular hypertonicity induces a set of osmocompensatory genes transcription, leading to the accumulation of gene products and osmolytes within the cells. TonEBP (Tonicity Element Binding Protein), has been identified as a transcription factor responsible for the hypertonic induction of osmocompensatory genes. The chromatin environment of a gene has a major influence on its transcription efficiency. The activation and repression of genes have been associated with alterations in chromatin structure. Several general mechanisms for altering更多还原