Kimball S R, Yancisin M, Horetsky R L, Jefferson L S
Department of Cellular and Molecular Physiology, Pennsylvania State University, Hershey 17033, USA.
Int J Biochem Cell Biol. 1996 Mar;28(3):285-94. doi: 10.1016/1357-2725(95)00143-3.
Protein synthesis is inhibited in both rat liver and isolated rat hepatocytes following deprivation of single essential amino acids. The aim of the present study was to define the time course of changes in peptide-chain initiation, albumin synthesis, and albumin mRNA following histidine deprivation and the reversal of these changes in response to readdition of the deprived amino acid. A further aim was to ascertain whether there was an accommodation of the inhibition of initiation following long-term amino acid deprivation. Primary cultures of rat hepatocytes were maintained in serum-free medium containing either all amino acids (complete medium) or all except histidine. Synthesis of total protein was reduced to 34% of control values following 48 hr of histidine deprivation and was restored to control values within 1 hr of addition of complete medium to histidine-deprived cells. These changes in protein synthesis were due to translational regulation involving initiation. No accommodation of the inhibition was observed following long-term deprivation of histidine as has been observed under other conditions of cellular stress. The synthesis of albumin was reduced to a greater extent than that of total protein, and required 72 hr to recover to control values following return to complete medium. These changes in albumin synthesis were due to a combination of altered initiation and a mechanism involving pretranslational regulation as evidenced by corresponding alterations in albumin mRNA. The results show that amino acid availability controls protein synthesis in liver cells through both translational and pretranslational mechanisms.
在单一必需氨基酸缺乏后，大鼠肝脏和分离的大鼠肝细胞中的蛋白质合成均受到抑制。本研究的目的是确定组氨酸缺乏后肽链起始、白蛋白合成和白蛋白mRNA变化的时间进程，以及补充缺乏的氨基酸后这些变化的逆转情况。另一个目的是确定长期氨基酸缺乏后起始抑制是否存在适应性变化。大鼠肝细胞原代培养物维持在含有所有氨基酸（完全培养基）或除组氨酸外所有氨基酸的无血清培养基中。组氨酸缺乏48小时后，总蛋白合成降至对照值的34%，在向缺乏组氨酸的细胞中添加完全培养基后1小时内恢复到对照值。蛋白质合成的这些变化是由于涉及起始的翻译调控。长期缺乏组氨酸后未观察到如在其他细胞应激条件下所观察到的起始抑制的适应性变化。白蛋白的合成比总蛋白减少的程度更大，恢复到完全培养基后需要72小时才能恢复到对照值。白蛋白合成的这些变化是由于起始改变和一种涉及翻译前调控的机制共同作用的结果，白蛋白mRNA的相应改变证明了这一点。结果表明，氨基酸可用性通过翻译和翻译前机制控制肝细胞中的蛋白质合成。
