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标题：Tissue-Specific Regulation of 4E-BP1 and S6K1 Phosphorylation by α-Ketoisocaproate
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作者：Fumiaki YOSHIZAWA ; Haruhito SEKIZAWA ; Sachiyo HIRAYAMA 等
期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2004
卷号：50
期号：1
页码：56-60
DOI：10.3177/jnsv.50.56
出版社：Center for Academic Publications Japan
摘要：The indispensable branched-chain amino acid leucine acts as a key regulator of mRNA translation by modulating the phosphorylation of proteins that represent impor-tant control points in translation initiation, including the translational repressor, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K1). In the current study, we compared the effects of L- and D-enantiomers of leucine on the phosphorylation of 4E-BP1 and S6K1. We also assessed whether leucine itself or its metabolite, α-ketoisocaproate (α-KIC), mediates the effects of leucine. Food-deprived (18h) rats were orally administered 135mg/100g body weight L-leucine, D-leucine or α-KIC and were sacrificed after 1h. L-Leucine administration had an obvious stimulatory effect on the phosphorylation of 4E-BP 1 and S6K1 in both skeletal muscle and liver while D-leucine was much less effective, indicating that the effect of leucine is stereospecific. Oral administration of α-KIC mimicked the stimulatory effect of L-leucine in skeletal muscle. In contrast to skel-etal muscle, provision of α-KIC was significantly less effective than L-leucine in the liver. The results showing that the efficacy of L-leucine and α-KIC in stimulating phosphorylation of S6K1 and 4E-BP 1 is equivalent in skeletal muscle, may be explained by the conversion of a-KIC to L-leucine.
关键词：leucine;α-ketoisocaproate;4E-BP1;S6K1;translation initiation