title: Local NSAID infusion does not affect protein synthesis and gene expression in human muscle after eccentric exercise.
abstract: Unaccustomed exercise leads to satellite cell proliferation and increased skeletal muscle protein turnover. Several growth factors and cytokines may be involved in the adaptive responses. Non-steroidal anti-inflammatory drugs (NSAIDs) negatively affect muscle regeneration and adaptation in animal models, and inhibit the exercise-induced satellite cell proliferation and protein synthesis in humans. However, the cellular mechanisms eliciting these responses remain unknown. Eight healthy male volunteers performed 200 maximal eccentric contractions with each leg. To block prostaglandin synthesis locally in the skeletal muscle, indomethacin (NSAID) was infused for 7.5 h via microdialysis catheters into m. vastus lateralis of one leg. Protein synthesis was determined by the incorporation of 1,2-(13) C(2) leucine into muscle protein from 24 to 28 h post-exercise. Furthermore, mRNA expression of selected genes was measured in muscle biopsies (5 h and 8 days post-exercise) by real-time reverse transcriptase PCR. Myofibrillar and collagen protein synthesis were unaffected by the local NSAID infusion. Five hours post-exercise, the mRNA expression of cyclooxygenase-2 (COX2) was sixfold higher in the NSAID leg (P=0.016) compared with the unblocked leg. The expression of growth factors and matrix-related genes were unaffected by NSAID. Although NSAIDs inhibit the exercise-induced satellite cell proliferation, we observed only limited effects on gene expression, and on post-exercise protein synthesis.
authors.affiliation: Institute of Sports Medicine, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. ullaramer@hotmail.com
authors.forename: U R
authors.initials: UR
authors.lastname: Mikkelsen
authors.forename: P
authors.initials: P
authors.lastname: Schjerling
authors.forename: I C
authors.initials: IC
authors.lastname: Helmark
authors.forename: S
authors.initials: S
authors.lastname: Reitelseder
authors.forename: L
authors.initials: L
authors.lastname: Holm
authors.forename: D
authors.initials: D
authors.lastname: Skovgaard
authors.forename: H
authors.initials: H
authors.lastname: Langberg
authors.forename: M
authors.initials: M
authors.lastname: Kjaer
authors.forename: K M
authors.initials: KM
authors.lastname: Heinemeier
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016326:Extracellular Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D009124:Muscle Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D051546:Cyclooxygenase 2; D007213:Indomethacin