Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth.

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  • Additional Information
    • Author-Supplied Keywords:
      Amniotes
      Anatomy
      Animal cells
      Animals
      Biochemistry
      Biology and life sciences
      Cell biology
      Cell differentiation
      Cellular types
      Developmental biology
      DNA-binding proteins
      Eukaryota
      Gene expression
      Gene regulation
      Genetics
      Mammals
      Medicine and health sciences
      Messenger RNA
      Morphogenesis
      Muscle differentiation
      Muscle fibers
      Muscles
      Musculoskeletal system
      Nucleic acids
      Organisms
      Proteins
      Regulatory proteins
      Research Article
      RNA
      Skeletal muscles
      Swine
      Transcription factors
      Vertebrates
    • NAICS/Industry Codes:
      112990 All Other Animal Production
    • Abstract:
      Previously, we highlighted induction of an integrated stress response (ISR) gene program in skeletal muscle of pigs treated with a beta-adrenergic agonist. Hence we tested the hypothesis that the ER-stress inhibitor, sodium 4-phenylbutyrate (PBA), would inhibit Clenbuterol-mediated muscle growth and reduce expression of genes that are known indicators of an ISR in mice. Clenbuterol (1mg/kg/day) administered to C57BL6/J mice for 21 days increased body weight (p<0.001), muscle weights (p<0.01), and muscle fibre diameters (p<0.05). Co-administration of PBA (100mg/kg/day) did not alter the Clenbuterol-mediated phenotype, nor did PBA alone have any effects compared to that of the vehicle treated mice. Clenbuterol increased skeletal muscle mRNA expression of phosphoserine amino transferase 1 (PSAT1, p<0.001) and cyclophillin A (p<0.01) at day 3, but not day 7. Clenbuterol decreased mRNA expression of activating transcription factor (ATF) 4 and ATF5 at day 3 (p<0.05) and day 7 (p<0.01), X-box binding protein 1 (XBP1) variant 2 mRNA at day 3 only (p<0.01) and DNA damage inducible transcript 3 (DDIT3/CHOP) mRNA at day 7 only (p<0.05). Co-administration of PBA had no effect on Clenbuterol-induced changes in skeletal muscle gene expression. In contrast, treatment of C2C12 myotubes with 5mM PBA (8hr) attenuated the thapsigargin-induced ISR gene program. Prolonged (24-48hr) treatment with PBA caused atrophy (p<0.01), reduced neoprotein synthesis (p<0.0001) and decreased expression of myogenin and fast myosin heavy chain genes (p<0.01), indicating an inhibition of myogenic differentiation. In summary, Clenbuterol did not induce an ISR gene program in mouse muscle. On the contrary, it reduced expression of a number of ISR genes, but it increased expression of PSAT1 mRNA. Co-administration of PBA had no effect on Clenbuterol-mediated muscle growth or gene expression in mice, whereas PBA did inhibit thapsigargin-induced ISR gene expression in cultured C2C12 cells and appeared to inhibit myogenic differentiation, independent of altering ISR gene expression. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom
      2School of Life Sciences, University of Nottingham, Medical School, Nottingham, United Kingdom
    • Full Text Word Count:
      8173
    • ISSN:
      1932-6203
    • Accession Number:
      10.1371/journal.pone.0201481
    • Accession Number:
      130955815
  • Citations
    • ABNT:
      BROWN, D. M. et al. Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth. PLoS ONE, [s. l.], v. 13, n. 7, p. 1–16, 2018. DOI 10.1371/journal.pone.0201481. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=a9h&AN=130955815&custid=s6224580. Acesso em: 10 dez. 2019.
    • AMA:
      Brown DM, Jones S, Daniel ZCTR, et al. Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth. PLoS ONE. 2018;13(7):1-16. doi:10.1371/journal.pone.0201481.
    • APA:
      Brown, D. M., Jones, S., Daniel, Z. C. T. R., Brearley, M. C., Lewis, J. E., Ebling, F. J. P., … Brameld, J. M. (2018). Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth. PLoS ONE, 13(7), 1–16. https://doi.org/10.1371/journal.pone.0201481
    • Chicago/Turabian: Author-Date:
      Brown, David M., Sarah Jones, Zoe C. T. R. Daniel, Madelaine C. Brearley, Jo E. Lewis, Francis J. P. Ebling, Tim Parr, and John M. Brameld. 2018. “Effect of Sodium 4-Phenylbutyrate on Clenbuterol-Mediated Muscle Growth.” PLoS ONE 13 (7): 1–16. doi:10.1371/journal.pone.0201481.
    • Harvard:
      Brown, D. M. et al. (2018) ‘Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth’, PLoS ONE, 13(7), pp. 1–16. doi: 10.1371/journal.pone.0201481.
    • Harvard: Australian:
      Brown, DM, Jones, S, Daniel, ZCTR, Brearley, MC, Lewis, JE, Ebling, FJP, Parr, T & Brameld, JM 2018, ‘Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth’, PLoS ONE, vol. 13, no. 7, pp. 1–16, viewed 10 December 2019, .
    • MLA:
      Brown, David M., et al. “Effect of Sodium 4-Phenylbutyrate on Clenbuterol-Mediated Muscle Growth.” PLoS ONE, vol. 13, no. 7, July 2018, pp. 1–16. EBSCOhost, doi:10.1371/journal.pone.0201481.
    • Chicago/Turabian: Humanities:
      Brown, David M., Sarah Jones, Zoe C. T. R. Daniel, Madelaine C. Brearley, Jo E. Lewis, Francis J. P. Ebling, Tim Parr, and John M. Brameld. “Effect of Sodium 4-Phenylbutyrate on Clenbuterol-Mediated Muscle Growth.” PLoS ONE 13, no. 7 (July 27, 2018): 1–16. doi:10.1371/journal.pone.0201481.
    • Vancouver/ICMJE:
      Brown DM, Jones S, Daniel ZCTR, Brearley MC, Lewis JE, Ebling FJP, et al. Effect of sodium 4-phenylbutyrate on Clenbuterol-mediated muscle growth. PLoS ONE [Internet]. 2018 Jul 27 [cited 2019 Dec 10];13(7):1–16. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=a9h&AN=130955815&custid=s6224580