Suppression of myofibrillar proteolysis in chick skeletal muscles by alpha-ketoisocaproate.
We previously reported that L-leucine suppresses myofibrillar proteolysis in chick skeletal muscles. In the current study, we compared the effects of L- and D-enantiomers of leucine on myofibrillar proteolysis in skeletal muscle of chicks. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (24 h) chicks were orally administered 225 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 2 h. L-Leucine administration had an obvious inhibitory effect on myofibrillar proteolysis (plasma N(tau)-methylhistidine concentration) in chicks while D-leucine and alpha-KIC were much more effective. We also examined the expression of the proteolytic-related genes (ubiquitin, proteasome, m-calpain and cathepsin B) by real-time PCR of cDNA in chick skeletal muscles. Ubiquitin mRNA expression was decreased by D-leucine and alpha-KIC but not L-leucine. Proteasome and m-calpain mRNA expressions as well as cathepsin B mRNA expression were likewise decreased by L-leucine, D-leucine and alpha-KIC. These results indicate that D-leucine and alpha-KIC suppress proteolytic-related genes, resulting in an decrease in myofibrillar proteolysis while L-leucine is much less effective in skeletal muscle of chicks, may be explain by conversion of D-leucine to alpha-KIC.
Nakashima
K
K
Department of Animal Physiology and Nutrition, National Institute of Livestock and Grassland Science, Tsukuba, Japan. kaznaka@affrc.go.jp
Yakabe
Y
Y
Ishida
A
A
Yamazaki
M
M
Abe
H
H
D000818:Animals; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D005508:Food Deprivation; D007651:Keto Acids / Q000378:metabolism*; D007930:Leucine / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008968:Molecular Conformation; D018482:Muscle, Skeletal / Q000166:cytology*; D009210:Myofibrils / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
D007651:Keto Acids; D025801:Ubiquitin; D012313:RNA; C013082:alpha-ketoisocaproic acid; D002154:Calpain; D046988:Proteasome Endopeptidase Complex; D007930:Leucine