Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs

作     者：Agus Suryawan Teresa A Davis 

作者机构：United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research CenterDepartment of PediatricsBaylor College of Medicine 

出 版 物：《Journal of Animal Science and Biotechnology》 (畜牧与生物技术杂志（英文版）)

年 卷 期：2014年第5卷第3期

页      面：299-309页

核心收录：

学科分类：0905[农学-畜牧学] 09[农学] 

基　　金：funded in part by National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant AR-044474(T.A.Davis) National Institute of Child Health and Human Development HD-072891(T.A.Davis) by the USDA/ARS under Cooperative Agreement no.6250-510000-055(T.A.Davis) 

主　　题：Amino acids Autophagy Insulin Leucine Muscle Neonate Protein degradation Protein synthesis,Swine Ubiquitin 

摘      要：Background： The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin and amino acids, especially leucine, modulate skeletal muscle protein synthesis and how this changes with development. In the current study, we identified mechanisms involved in protein degradation regulation. In experiment 1,6- and 26-d-old pigs were studied during 1） euinsulinemic-euglycemic-euaminoacidemic, 2） euinsulinemic-euglycemiohyperaminoacidemic, and 3） hyperinsulinemic-euglycemic-euaminoacidemic clamps for 2 h. In experiment 2, 5-d-old pigs were studied during 1） euinsulinemic-euglycemic-euaminoacidemic-euleucinemic, 2） euinsulinemic-euglycemic-hypoaminoacidemic- hyperleucinemic, and 3） euinsulinemic-euglycemic-euaminoacidemic-hyperleucinemic clamps for 24 h. We determined in muscle indices of ubiquitin-proteasome, i.e., atrogin-1 （MAFbx） and muscle RING-finger protein-1 （MuRF1） and autophagy-lysosome systems, i.e., unc51-1ike kinase 1 （UKL1）, microtubule-associated protein light chain 3 （LC3）, and lysosomal-associated membrane protein 2 （Lamp-2）. For comparison, we measured ribosomal protein 56 （rpS6） and eukaryotic initiation factor 4E （elF4E） activation, components of translation initiation. Results： Abundance of atrogin-1, but not MuRF1, was greater in 26- than 6-d-old pigs and was not affected by insulin, amino acids, or leucine. Abundance of ULK1 and LC3 was higher in younger pigs and not affected by treatment. The LC3-11/LC3-1 ratio was reduced and ULK1 phosphorylation increased by insulin, amino acids, and leucine. These responses were more profound in younger pigs. Abundance of Lamp-2 was not affected by treatment or development. Abundance of elF4E, but not rpS6, was higher in 6- than 26-d-old-pigs but unaffected by treatment. Phosphorylation of elF4E was not affected by treatment, however, insulin, amino acids, and leucine stimulated rpS6 phosphorylation, and the resp