The gene expression of numerous SLC transporters is altered in the immortalized hypothalamic cell line N25/2 following amino acid starvation

Amino acids are known to play a key role in gene expression regulation,and in mammalian cells, amino acid signaling is mainly mediated via twopathways, the mammalian target of rapamycin complex 1 (mTORC1) pathwayand the amino acid responsive (AAR) pathway. It is vital for cells tohave a system to sense amino acid levels, in order to control protein andamino acid synthesis and catabolism. Amino acid transporters are crucialin these pathways, due to both their sensing and transport functions. Inthis large-scale study, an immortalized mouse hypothalamic cell line (N25/2)was used to study the gene expression changes following 1, 2, 3, 5 or 16 hof amino acid starvation. We focused on genes encoding solute carriers(SLCs) and putative SLCs, more specifically on amino acid transporters.The microarray contained 28 270 genes and 86.2% of the genes wereexpressed in the cell line. At 5 h of starvation, 1001 genes were upregulatedand 848 genes were downregulated, and among these, 47 genes from theSLC superfamily or atypical SLCs were found. Of these, 15 were genesencoding amino acid transporters and 32 were genes encoding other SLCsor atypical SLCs. Increased expression was detected for genes encodingamino acid transporters from system A, ASC, L, N, T, xc-, and y+. UsingGO annotations, genes involved in amino acid transport and amino acidtransmembrane transporter activity were found to be most upregulated at3 h and 5 h of starvation