Insulin down-regulates the expression of ubiquitin E3 ligases partially by inhibiting the activity and expression of AMP-activated protein kinase in L6 myotubes
| Autor: | Chuanan Shen, Chi Yunfei, Xi-bo Zhang, Jia-ke Chai, Tian-jun Sun, Qing-gang Hu, Ning Dong, Li Ma, Huping Deng |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
insulin medicine.medical_treatment Ubiquitin-Protein Ligases Muscle Fibers Skeletal Biophysics Down-Regulation Muscle Proteins Biology Protein degradation AMP-Activated Protein Kinases muscle RING finger 1 (MuRF1) Biochemistry Gene Expression Regulation Enzymologic Cell Line Tripartite Motif Proteins AMP-activated protein kinase Downregulation and upregulation Internal medicine AMP-activated protein kinase (AMPK) medicine Animals Protein kinase A Molecular Biology Protein kinase B muscle atrophy F-box (MAFbx) Original Paper SKP Cullin F-Box Protein Ligases Insulin AMPK Skeletal muscle Cell Biology Ribonucleotides Aminoimidazole Carboxamide Original Papers Rats medicine.anatomical_structure Endocrinology myotubes biology.protein |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 |
| Popis: | We conclude that insulin inhibits AMPK through Akt phosphorylation in L6 myotubes, which may serve as a possible signalling pathway for the down-regulation of protein degradation. Besides, decreased expression of AMPK α2 may partially participate in inhibiting the activity of AMPK. While insulin is an anabolic hormone, AMP-activated protein kinase (AMPK) is not only a key energy regulator, but it can also control substrate metabolism directly by inducing skeletal muscle protein degradation. The hypothesis of the present study was that insulin inhibits AMPK and thus down-regulates the expression of the ubiquitin E3 ligases, muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in skeletal muscle cells. Differentiated L6 myotubes were treated with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) and/or compound C to stimulate and/or block AMPK respectively. These treatments were also conducted in the presence or absence of insulin and the cells were analysed by western blot and quantitative real-time PCR. In addition, nuleotide levels were determined using HPLC. The activation of AMPK with AICAR enhanced the mRNA levels of MAFbx and MuRF1. Insulin reduced the phosphorylation and activity AMPK, which was accompanied by reduced MAFbx and MuRF1 mRNA levels. Using a protein kinase B (PKB/Akt) inhibitor, we found that insulin regulates AMPK through the activation of Akt. Furthermore, insulin down-regulated AMPK α2 mRNA. We conclude that insulin inhibits AMPK through Akt phosphorylation in L6 myotubes, which may serve as a possible signalling pathway for the down-regulation of protein degradation. In addition, decreased expression of AMPK α2 may partially participate in inhibiting the activity of AMPK. |
| Databáze: | OpenAIRE |
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