Antioxidant action of L-alanine: heme oxygenase-1 and ferritin as possible mediators

Biochem Biophys Res Commun. 2004 Feb 6;314(2):351-5. doi: 10.1016/j.bbrc.2003.12.089.


The amino acid L-alanine has been shown to exert long-term cytoprotection by as yet unidentified molecular mechanisms. Using cultured human endothelial cells (ECV 304), the present study investigates the effect of L-alanine on hydrogen peroxide-mediated cytotoxicity and expression of the antioxidant stress proteins, heme oxygenase-1 (HO-1) and ferritin. Pretreatment with L-alanine (0.3-3mM) protected endothelial cells from hydrogen peroxide-dependent cytotoxicity and increased the surviving endothelial cell fraction by 76%. The described protection was associated with a significant induction of heme oxygenase activity and ferritin protein synthesis. A protective effect similar to L-alanine was observed when preincubating the cells with iron-free apoferritin or the antioxidant HO-1 product, bilirubin. The present study demonstrates that L-alanine stimulates expression of the antioxidant defense proteins HO-1 and ferritin in endothelial cells. Increased heme oxygenase activity and ferritin expression improve endothelial dysfunction suggesting an antiatherogenic potential of L-alanine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / metabolism*
  • Alanine / pharmacology
  • Antioxidants / pharmacology*
  • Apoferritins / pharmacology
  • Bilirubin / metabolism
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology
  • Endothelium, Vascular / metabolism
  • Ferritins / biosynthesis
  • Ferritins / metabolism*
  • Ferritins / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase-1
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Membrane Proteins
  • Oxidants / pharmacology


  • Antioxidants
  • Membrane Proteins
  • Oxidants
  • Ferritins
  • Apoferritins
  • Hydrogen Peroxide
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Alanine
  • Bilirubin