Antioxidant action of L-alanine: heme oxygenase-1 and ferritin as possible mediators.
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.
Grosser
Nina
N
Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, 06120 Wolfgang-Langenbeck-Str. 4, Halle (Saale), Germany. grosser@pharmazie.uni-halle.de
Oberle
Stefanie
S
Berndt
Georg
G
Erdmann
Kati
K
Hemmerle
Anke
A
Schröder
Henning
H
D000409:Alanine / Q000378:metabolism* / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001052:Apoferritins / Q000494:pharmacology; D001663:Bilirubin / Q000378:metabolism; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism; D005293:Ferritins / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008565:Membrane Proteins; D016877:Oxidants / Q000494:pharmacology
D000975:Antioxidants; D008565:Membrane Proteins; D016877:Oxidants; D005293:Ferritins; D001052:Apoferritins; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D000409:Alanine; D001663:Bilirubin