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.
Tesseraud
Sophie
S
INRA, UR83 Recherches Avicoles, F-37380 Nouzilly, France. tesserau@tours.inra.fr
Métayer-Coustard
Sonia
S
Boussaid
Sourour
S
Crochet
Sabine
S
Audouin
Estelle
E
Derouet
Michel
M
Seiliez
Iban
I
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000008:administration & dosage*; D009124:Muscle Proteins / Q000378:metabolism*; D011784:Quail; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D000596:Amino Acids; D007328:Insulin; D009124:Muscle Proteins; C486691:Fbxo32 protein, mouse; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases