期刊
AMINO ACIDS
卷 37, 期 1, 页码 79-88出版社
SPRINGER WIEN
DOI: 10.1007/s00726-008-0199-2
关键词
SNAT2; System A; Nutrient starvation; Amino acid transport; ATF4; eIF2
资金
- Institute of Diabetes, Digestive and Kidney Diseases, the National Institutes of Health [DK-70647, DK-52064]
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 2 alpha (eIF2 alpha) phosphorylation and ATF4 translation. When HepG2 cells were deprived of an individual essential amino acid, p-eIF2 alpha 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.
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