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 two pathways, the mammalian target of rapamycin complex 1 (mTORC1) pathway and the amino acid responsive (AAR) pathway. It is vital for cells to have a system to sense amino acid levels, in order to control protein and amino acid synthesis and catabolism. Amino acid transporters are crucial in these pathways, due to both their sensing and transport functions. In this 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 h of 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 were expressed in the cell line. At 5 h of starvation, 1001 genes were upregulated and 848 genes were downregulated, and among these, 47 genes from the SLC superfamily or atypical SLCs were found. Of these, 15 were genes encoding amino acid transporters and 32 were genes encoding other SLCs or atypical SLCs. Increased expression was detected for genes encoding amino acid transporters from system A, ASC, L, N, T, xc-, and y+. Using GO annotations, genes involved in amino acid transport and amino acid transmembrane transporter activity were found to be most upregulated at 3 h and 5 h of starvation.