Small Molecular Weight Soybean Protein-Derived Peptides Nutriment Attenuates Rat Burn Injury-Induced Muscle Atrophy by Modulation of Ubiquitin-Proteasome System and Autophagy Signaling Pathway

J Agric Food Chem. 2018 Mar 21;66(11):2724-2734. doi: 10.1021/acs.jafc.7b05387. Epub 2018 Mar 8.

Abstract

This article describes results of the effect of dietary supplementation with small molecular weight soybean protein-derived peptides on major rat burn injury-induced muscle atrophy. As protein nutrients have been previously implicated to play an important role in improving burn injury outcomes, optimized more readily absorbed small molecular weight soybean protein-derived peptides were evaluated. Thus, the quantity, sodium dodecyl sulfate polyacrylamide-gel electrophoresis patterns, molecular weight distribution, and composition of amino acids of the prepared peptides were analyzed, and a major full-thickness 30% total body surface area burn-injury rat model was utilized to assess the impact of supplementation with soybean protein-derived peptides on initial systemic inflammatory responses as measured by interferon-gamma (IFN-γ), chemokine (C-C motif) ligand 2 (CCL2, also known as MCP-1), chemokine (C-C motif) ligand 7 (CCL7, also known as MCP-3), and generation of muscle atrophy as measured by tibialis anterior muscle (TAM) weight relative to total body weight. Induction of burn injury-induced muscle atrophy ubiquitin-proteasome system (UPS) signaling pathways in effected muscle tissues was determined by Western blot protein expression measurements of E3 ubiquitin-protein ligase TRIM-63 (TRIM63, also known as MuRF1) and F-box only protein 32 (FBXO32, also known as atrogin-1 or MAFbx). In addition, induction of burn injury-induced autophagy signaling pathways associated with muscle atrophy in effected muscle tissues was assessed by immunohistochemical analysis as measured by microtubule-associated proteins 1 light chain 3 (MAP1LC3, or commonly abbreviated as LC3) and beclin-1 (BECN1) expression, as well as relative induction of cytoplasmic-liberated form of MAP1LC3 (LC3-I) and phagophore and autophagosome membrane-bound form of MAP1LC3 (LC3-II), and BECN1 protein expression by Western blot analysis. Nutrient supplementation with small molecular weight soybean protein-derived peptides resulted a significant reduction in burn injury-induced inflammatory markers, muscle atrophy, induction of TRIM63 and FBXO32 muscle atrophy signaling pathways, and induction of autophagy signaling pathways LC3 and BECN1 associated with muscle atrophy. These results implicated that small molecular weight soybean-derived peptides dietary supplementation could be used as an adjunct therapy in burn injury management to reduce the development or severity of muscle atrophy for improved burn patient outcomes.

Keywords: autophagy; burn; muscle atrophy; soybean protein-derived peptides; ubiquitin−proteasome system.

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Burns / complications*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Male
  • Molecular Weight
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / physiopathology
  • Peptides / administration & dosage*
  • Peptides / chemistry
  • Proteasome Endopeptidase Complex / metabolism*
  • Rats
  • Soybean Proteins / administration & dosage
  • Soybean Proteins / chemistry*
  • Ubiquitin / metabolism*

Substances

  • Beclin-1
  • Chemokine CCL2
  • Peptides
  • Soybean Proteins
  • Ubiquitin
  • Interferon-gamma
  • Proteasome Endopeptidase Complex