Insulin down-regulates ubiquitin E3 ligases expression by inhibiting activity and expression of AMP-

• 作 者: Hu-Ping Deng Jia-Ke Chai Xi-Bo Zhang Li Ma Chuan-An Shen
• 机 构: Department of Burn and Plastic Surgery,Burns Institute,Burn and Plastic Hospital,First Affiliated Ho
• 出 处: 2013年全军烧伤外科学术年会
• 发表日期: 2013年12期

　　Insulin and glucocorticoid are two hormones distinctly regulating anabolism and catabolism in contrary ways in skeletal muscle.AMP-activated protein kinase (AMPK)is not only a key energy regulator, but also regulates substance metabolism directly,such as inducing skeletal muscle protein degradation.The hypothesis of the present study was that insulin and glucocorticoid regulate AMPK α contrarily in skeletal muscle cells, consequently regulating ubiquitin E3 ligases, Muscle Atrophy F-box (MAFbx) and Muscle RING finger 1 (MuRF1).In differentiated L6 myotubes, activation of AMPK with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR)enhanced mRNA expression of MAFbx and MuRF1 with Quantitative Real Time PCR (Q-PCR).Insulin dephosphorylated and inhibited AMPK with western-blotting analysis of phospho-AMPK and phospho-ACC, accompanied with decreasing mRNA levels of MAFbx, while dexmethasone phosphorylated AMPK α and increased MAFbx and MuRFi mRNA levels.Interestingly, dexmethasone inhibited AMPK activity.By using PI3K inhibitor and Akt inhibitor (Wortmannin or Akt inhibitor Ⅳ respectively), we found that insulin regulated AMPK α through activation of Akt (PKB).Both insulin and dexmethasone down-regulated mRNA level of AMPK α 2.Insulin still reduced mRNA levels of AMPK upstream kinase (LKB1).We conclude that insulin inhibits AMPK through phophorylation of Akt in L6 myotubes, which may serve as another signaling pathway in down-regulating protein degradation aside from Akt-Foxo pathway.However,dexmethasone induces protein degradation not through regulating AMPK.