Glycine stimulates protein synthesis and inhibits oxidative stress in pig small intestinal epithelial cells

J Nutr. 2014 Oct;144(10):1540-8. doi: 10.3945/jn.114.194001. Epub 2014 Aug 13.


Glycine has recently been classified as a nutritionally essential amino acid for maximal growth in young pigs. Currently, little is known about the metabolism or function of glycine in the neonatal intestine. This work was conducted to test the hypothesis that glycine has a protective effect against oxidative stress in intestinal epithelial cells. Jejunal enterocytes isolated from newborn pigs were cultured in the presence of 0.0-2 mmol/L glycine for measurements of glycine metabolism, cell proliferation, protein turnover, apoptosis, and antioxidative response. Compared with 0.0-0.5 mmol/L glycine, 1.0 mmol/L glycine enhanced (P < 0.05) cell growth (by 8-24% on day 2 and by 34-224% on day 4, respectively) and protein synthesis (by 36-419%) while reducing (P < 0.05) protein degradation (by 7-28%). This effect of glycine was associated with activation of the mammalian target of rapamycin signaling pathway in enterocytes. By using a model of oxidative stress induced by 30 μmol/L 4-hydroxynonenal (4-HNE), which was assessed by flow cytometry analysis, 1.0 mmol/L glycine inhibited (P < 0.05) activation of caspase 3 by 25% and attenuated (P < 0.05) 4-HNE-induced apoptosis by 38% in intestinal porcine epithelial cell line 1 cells through promotion of reduced glutathione synthesis and expression of glycine transporter 1 while reducing the activation of extracellular signal-regulated kinases, c-Jun amino-terminal kinases, and p38 protein in the mitogen-activated protein kinase signaling pathway. These novel findings provide a biochemical mechanism for the use of dietary glycine to improve intestinal health in neonates under conditions of oxidative stress and glycine deficiency.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehydes / toxicity
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glutathione / biosynthesis
  • Glycine / pharmacology*
  • Glycine Plasma Membrane Transport Proteins / genetics
  • Glycine Plasma Membrane Transport Proteins / metabolism
  • Intestine, Small / cytology*
  • Intestine, Small / drug effects
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Oxidative Stress / drug effects*
  • Phosphorylation
  • Protein Biosynthesis / drug effects*
  • Signal Transduction
  • Swine
  • TOR Serine-Threonine Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Aldehydes
  • Glycine Plasma Membrane Transport Proteins
  • TOR Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • Glutathione
  • 4-hydroxy-2-nonenal
  • Glycine