title: Skeletal muscle amino acid transporter expression is increased in young and older adults following resistance exercise.
abstract: Amino acid transporters and mammalian target of rapamycin complex 1 (mTORC1) signaling are important contributors to muscle protein anabolism. Aging is associated with reduced mTORC1 signaling following resistance exercise, but the role of amino acid transporters is unknown. Young (n = 13; 28 ± 2 yr) and older (n = 13; 68 ± 2 yr) subjects performed a bout of resistance exercise. Skeletal muscle biopsies (vastus lateralis) were obtained at basal and 3, 6, and 24 h postexercise and were analyzed for amino acid transporter mRNA and protein expression and regulators of amino acid transporter transcription utilizing real-time PCR and Western blotting. We found that basal amino acid transporter expression was similar in young and older adults (P > 0.05). Exercise increased L-type amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, sodium-coupled neutral amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, and cationic amino acid transporter 1/SLC7A1 mRNA expression in both young and older adults (P < 0.05). L-type amino acid transporter 1 and CD98 protein increased only in younger adults (P < 0.05). eukaryotic initiation factor 2 α-subunit (S52) increased similarly in young and older adults postexercise (P < 0.05). Ribosomal protein S6 (S240/244) and activating transcription factor 4 nuclear protein expression tended to be higher in the young, while nuclear signal transducer and activator of transcription 3 (STAT3) (Y705) was higher in the older subjects postexercise (P < 0.05). These results suggest that the rapid upregulation of amino acid transporter expression following resistance exercise may be regulated differently between the age groups, but involves a combination of mTORC1, activating transcription factor 4, eukaryotic initiation factor 2 α-subunit, and STAT3. We propose an increase in amino acid transporter expression may contribute to enhanced amino acid sensitivity following exercise in young and older adults. In older adults, the increased nuclear STAT3 phosphorylation may be indicative of an exercise-induced stress response, perhaps to export amino acids from muscle cells.
authors.affiliation: University of Texas Medical Branch, Department of Nutrition and Metabolism, Division of Rehabilitation Sciences, Sealy Center on Aging, 301 Univ. Blvd., Galveston, TX 77555-1144, USA. mjdrummo@utmb.edu
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Drummond
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.forename: Erin L
authors.initials: EL
authors.lastname: Glynn
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Timmerman
authors.forename: Jared M
authors.initials: JM
authors.lastname: Dickinson
authors.forename: Dillon K
authors.initials: DK
authors.lastname: Walker
authors.forename: David M
authors.initials: DM
authors.lastname: Gundermann
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000704:Analysis of Variance; D001706:Biopsy; D015153:Blotting, Western; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009119:Muscle Contraction; D010649:Phenylalanine / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D052097:Quadriceps Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D055070:Resistance Training; D038601:Ribosomal Protein S6 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
chemical_list: C497109:ATF4 protein, human; D026905:Amino Acid Transport Systems; D000596:Amino Acids; D015852:Eukaryotic Initiation Factor-2; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051701:Activating Transcription Factor 4; D010649:Phenylalanine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D007930:Leucine