Insulin and amino acid availability regulate atrogin-1 in avian QT6 cells.

New evidence has demonstrated that the expression of major genes, termed atrogenes, controls the ubiquitin-proteasome proteolytic pathway. The present work aimed to study the impact of insulin and amino acids on the expression of one of these atrogenes, the E3 ubiquitin ligase Muscle Atrophy F box (MAFbx, also called atrogin-1), in quail muscle (QT6) fibroblasts. First, we characterized atrogin-1 in QT6 cells and demonstrated the insulin sensitivity of these cells. Second, we showed that insulin reduced atrogin-1 mRNA via the phosphatidylinositol-3'kinase (PI3K)/protein kinase B (PKB or AKT)/target of rapamycin (TOR) pathway. Atrogin-1 expression also depended on the availability of an individual amino acid, i.e., methionine. Moreover, the amino acid-induced reduction of atrogin-1 was inhibited by rapamycin, indicating the involvement of the TOR pathway in such regulation. In conclusion, expression of the ubiquitin ligase atrogin-1 is regulated by both insulin and amino acids through the TOR pathway.