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首页> 外文期刊>American Journal of Physiology >Amino acid depletion activates TonEBP and sodium-coupled inositol transport.
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Amino acid depletion activates TonEBP and sodium-coupled inositol transport.

机译：氨基酸消耗会激活TonEBP和钠耦合的肌醇转运。

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摘要

The expression of the osmosensitive sodium/myo-inositol cotransporter (SMIT) is regulated by multiple tonicity-responsive enhancers (TonEs) in the 5'-flanking region of the gene. In response to hypertonicity, the nuclear abundance of the transcription factor TonE-binding protein (TonEBP) is increased, and the transcription of the SMIT gene is induced. Transport system A for neutral amino acids, another osmosensitive mechanism, is progressively stimulated if amino acid substrates are not present in the extracellular compartment. Under this condition, as in hypertonicity, cells shrink and mitogen-activated protein kinases are activated. We demonstrate here that a clear-cut nuclear redistribution of TonEBP, followed by SMIT expression increase and inositol transport activation, is observed after incubation of cultured human fibroblasts in Earle's balanced salts (EBSS), an isotonic, amino acid-free saline. EBSS-induced SMIT stimulation is prevented by substrates of system A, although these compounds do notcompete with inositol for transport through SMIT. We conclude that the incubation in isotonic, amino acid-free saline triggers an osmotic stimulus and elicits TonEBP-dependent responses like hypertonic treatment.
机译：渗透敏感性钠/肌醇共转运蛋白（SMIT）的表达受基因的5'侧翼区域的多个张力反应增强剂（TonEs）调节。响应高渗性，转录因子TonE结合蛋白（TonEBP）的核丰度增加，并且诱导了SMIT基因的转录。如果在细胞外区室中不存在氨基酸底物，则会逐渐刺激另一种对渗透敏感的中性氨基酸转运系统A。在这种情况下，如高渗性一样，细胞萎缩并激活丝裂原活化的蛋白激酶。我们在这里证明，在Earle的平衡盐（EBSS）（一种等渗的，不含氨基酸的盐水）中培养培养的人成纤维细胞后，可以观察到TonEBP的明确核再分布，然后是SMIT表达增加和肌醇转运激活。 EBSS诱导的SMIT刺激被系统A的底物阻止，尽管这些化合物不与肌醇竞争通过SMIT转运。我们得出的结论是，在等渗，不含氨基酸的盐水中孵育会触发渗透刺激，并引起TonEBP依赖性反应，如高渗治疗。

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