title: Leucine suppresses myofibrillar proteolysis by down-regulating ubiquitin-proteasome pathway in chick skeletal muscles.
abstract: In skeletal muscle, amino acids, together with hormones, are key regulators of protein metabolism. Leucine, in particular, has inhibitory effects of protein degradation in skeletal muscles, but the mechanisms are poorly understood. The present study addressed the role of leucine as a regulator of myofibrillar proteolysis in cultured chick myotubes and chick skeletal muscles, and aimed to determine which cellular responses regulate the process. In chick myotubes, leucine suppressed myofibrillar proteolysis (as measured by N(tau)-methylhistidine release), while also decreasing ubiquitin and proteasome C2 subunit mRNA. Oral administration of leucine also suppressed myofibrillar proteolysis (as measured by plasma N(tau)-methylhistidine concentration), while also decreasing proteasome C2 subunit mRNA in chick skeletal muscle. Leucine activated the phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) (but not the mammalian target of rapamycin) inhibition of these pathways and increased myofibrillar proteolysis, ubiquitin and proteasome C2 subunit mRNA. Thus, an important component of muscle proteolysis inhibition by leucine, through the PI3K and PKC, is its ability to suppress transcription of the ubiquitin and proteasome C2 subunit, and degradation of myofibrillar protein.
authors.affiliation: Department of Animal Physiology and Nutrition, National Institute of Livestock and Grassland Science, Tsukuba 305-0901, Japan. kaznaka@affrc.go.jp
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakashima
authors.forename: Aiko
authors.initials: A
authors.lastname: Ishida
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D007930:Leucine / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; D007930:Leucine