title: Serum from human burn victims impairs myogenesis and protein synthesis in primary myoblasts.
abstract: The pathophysiological response to a severe burn injury involves a robust increase in circulating inflammatory/endocrine factors and a hypermetabolic state, both of which contribute to prolonged skeletal muscle atrophy. In order to characterize the role of circulating factors in muscle atrophy following a burn injury, human skeletal muscle satellite cells were grown in culture and differentiated to myoblasts/myotubes in media containing serum from burn patients or healthy, age, and sex-matched controls. While incubation in burn serum did not affect NFκB signaling, cells incubated in burn serum displayed a transient increase in STAT3 phosphorlyation (Tyr705) after 48 h of treatment with burn serum (≈ + 70%; P < 0.01), with these levels returning to normal by 96 h. Muscle cells differentiated in burn serum displayed reduced myogenic fusion signaling (phospho-STAT6 (Tyr641), ≈-75%; ADAM12, ≈-20%; both P < 0.01), and reduced levels of myogenin (≈-75%; P < 0.05). Concomitantly, myotubes differentiated in burn serum demonstrated impaired myogenesis (assessed by number of nuclei/myotube). Incubation in burn serum for 96 h did not increase proteolytic signaling (assessed via caspase-3 and ubiquitin levels), but reduced anabolic signaling [p-p70S6k (Ser421/Thr424), -30%; p-rpS6 (Ser240/244), ≈-50%] and impaired protein synthesis (-24%) (P < 0.05). This resulted in a loss of total protein content (-18%) and reduced cell size (-33%) (P < 0.05). Overall, incubation of human muscle cells in serum from burn patients results in impaired myogenesis and reduced myotube size, indicating that circulating factors may play a significant role in muscle loss and impaired muscle recovery following burn injury.
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Corrick
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham Birmingham, AL, USA ; UAB Center for Exercise Medicine, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stec
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham Birmingham, AL, USA ; UAB Center for Exercise Medicine, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Merritt
authors.affiliation: UAB Center for Exercise Medicine, University of Alabama at Birmingham Birmingham, AL, USA ; Department of Surgery, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Windham
authors.affiliation: Department of Surgery, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Thomas
authors.affiliation: Department of Surgery, University of Texas Health Science Center Houston, TX, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Cross
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham Birmingham, AL, USA ; UAB Center for Exercise Medicine, University of Alabama at Birmingham Birmingham, AL, USA ; Geriatric Research, Education, and Clinical Center, Birmingham VA Medical Center Birmingham, AL, USA.
authors.forename: Marcas M
authors.initials: MM
authors.lastname: Bamman
keywords: burn; inflammation; muscle protein synthesis; myoblast; myogenesis; myotube