title: Post-exercise impact of ingested whey protein hydrolysate on gene expression profiles in rat skeletal muscle: activation of extracellular signal-regulated kinase 1/2 and hypoxia-inducible factor-1α.
abstract: We have previously shown that whey protein hydrolysate (WPH) causes a greater increase in muscle protein synthesis than does a mixture of amino acids that is identical in amino acid composition. The present study was conducted to investigate the effect of WPH on gene expression. Male Sprague-Dawley rats subjected to a 2 h swimming exercise were administered either a carbohydrate-amino acid diet or a carbohydrate-WPH diet immediately after exercise. At 1 h after exercise, epitrochlearis muscle mRNA was sampled and subjected to DNA microarray analysis. We found that ingestion of WPH altered 189 genes after considering the false discovery rate. Among the up-regulated genes, eight Gene Ontology (GO) terms were enriched, which included key elements such as Cd24, Ccl2, Ccl7 and Cxcl1 involved in muscle repair after exercise. In contrast, nine GO terms were enriched in gene sets that were down-regulated by the ingestion of WPH, and these GO terms fell into two clusters, 'regulation of ATPase activity' and 'immune response'. Furthermore, we found that WPH activated two upstream proteins, extracellular signal-regulated kinase 1/2 (ERK1/2) and hypoxia-inducible factor-1α (HIF-1α), which might act as key factors for regulating gene expression. These results suggest that ingestion of WPH, compared with ingestion of a mixture of amino acids with an identical amino acid composition, induces greater changes in the post-exercise gene expression profile via activation of the proteins ERK1/2 and HIF-1α.
authors.affiliation: Food Science Research Laboratories, Meiji Company Limited, 540 Naruda,Odawara, Kanagawa 250-0862, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kanda
authors.affiliation: Department of Applied Biological Chemistry,Graduate School of Agricultural and Life Sciences, The University of Tokyo,1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishijima
authors.affiliation: Project on Health and Anti-aging, Kanagawa Academy of Science and Technology, Life Science and Environment Research Center4F C-4, 3-25-13Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
authors.forename: Fumika
authors.initials: F
authors.lastname: Shinozaki
authors.affiliation: Food Science Research Laboratories, Meiji Company Limited, 540 Naruda,Odawara, Kanagawa 250-0862, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Food Science Research Laboratories, Meiji Company Limited, 540 Naruda,Odawara, Kanagawa 250-0862, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fukasawa
authors.affiliation: Department of Applied Biological Chemistry,Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Department of Applied Biological Chemistry,Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
authors.affiliation: Food Science Research Laboratories, Meiji Company Limited, 540 Naruda,Odawara, Kanagawa 250-0862, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawahata
authors.affiliation: Food Science Research Laboratories, Meiji Company Limited, 540 Naruda,Odawara, Kanagawa 250-0862, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ikegami
mesh_terms: D000818:Animals; D001628:Beverages; D004789:Enzyme Activation; D005526:Food, Formulated; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D008894:Milk Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011492:Protein Hydrolysates / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067816:Whey Proteins
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008894:Milk Proteins; D009124:Muscle Proteins; D011492:Protein Hydrolysates; D012333:RNA, Messenger; D000067816:Whey Proteins; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3