Palii S S, Kays C E, Deval C, Bruhat A, Fafournoux P, Kilberg M S
Department of Biochemistry and Molecular Biology, Genetics Institute, Shands Cancer Center and Center for Nutritional Sciences, University of Florida, College of Medicine, Box 100245, Gainesville, FL 32610-0245, USA.
Amino Acids. 2009 May;37(1):79-88. doi: 10.1007/s00726-008-0199-2. Epub 2008 Nov 14.
Amino acid deprivation activates the amino acid response (AAR) pathway that enhances transcription of genes containing an amino acid response element (AARE). The present data reveal a quantitative difference in the response to deprivation of individual amino acids. The AAR leads to increased eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation and ATF4 translation. When HepG2 cells were deprived of an individual essential amino acid, p-eIF2alpha and activating transcription factor 4 were increased, but the correlation was relatively weak. Complete amino acid starvation in either Earle's balanced salt solution or Krebs-Ringer bicarbonate buffer (KRB) resulted in activation of transcription driven by a SNAT2 genomic fragment that contained an AARE. However, for the KRB, a proportion of the transcription was AARE-independent suggesting that amino acid-independent mechanisms were responsible. Therefore, activation of AARE-driven transcription is triggered by a deficiency in any one of the essential amino acids, but the response is not uniform. Furthermore, caution must be exercised when using a medium completely devoid of amino acids.
氨基酸剥夺会激活氨基酸反应（AAR）途径，该途径会增强含有氨基酸反应元件（AARE）的基因的转录。目前的数据揭示了对单个氨基酸剥夺反应的定量差异。AAR会导致真核起始因子2α（eIF2α）磷酸化增加以及激活转录因子4（ATF4）的翻译增加。当HepG2细胞被剥夺单个必需氨基酸时，磷酸化的eIF2α（p-eIF2α）和激活转录因子4会增加，但相关性相对较弱。在Earle平衡盐溶液或 Krebs-Ringer碳酸氢盐缓冲液（KRB）中完全氨基酸饥饿会导致由包含AARE的SNAT2基因组片段驱动的转录激活。然而，对于KRB，一部分转录是不依赖AARE的，这表明存在不依赖氨基酸的机制。因此，任何一种必需氨基酸的缺乏都会触发AARE驱动的转录激活，但反应并不一致。此外，在使用完全不含氨基酸的培养基时必须谨慎。
