ACE Inhibitory Dipeptide Met-Tyr Diminishes Free Radical Formation in Human Endothelial Cells via Induction of Heme Oxygenase-1 and Ferritin

• Published in: The Journal of nutrition Vol. 136; no. 8; pp. 2148 - 2152
• Main Authors: Erdmann, Kati, Grosser, Nina, Schipporeit, Katrin, Schröder, Henning
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.08.2006; American Society for Nutritional Sciences
• Subjects: Angiotensin-Converting Enzyme Inhibitors; Angiotensin-Converting Enzyme Inhibitors - pharmacology; angiotensin-I converting enzyme; antihypertensive effect; bilirubin; biochemical pathways; Biological and medical sciences; biosynthesis; Cells, Cultured; cultured cells; dipeptides; Dipeptides - pharmacology; drug effects; endothelial cells; Endothelium, Vascular; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; enzyme activity; Enzyme Induction; Enzyme Induction - drug effects; enzyme inhibitors; Feeding. Feeding behavior; ferritin; Ferritins; Ferritins - biosynthesis; free radicals; Fundamental and applied biological sciences. Psychology; heme oxygenase (biliverdin-producing); heme oxygenase (decyclizing); Heme Oxygenase-1; Heme Oxygenase-1 - biosynthesis; Humans; metabolism; Methionine; NADP (coenzyme); oxidation; Oxidative Stress; Oxidative Stress - drug effects; peptidases; pharmacology; Reactive Oxygen Species; Reactive Oxygen Species - metabolism; Tyrosine; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Endothelial cell; Nutrition; Enzyme; Induction; Ferritin; Dipeptides; Heme oxygenase (decyclizing); Oxidoreductases; Free radical
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/136.8.2148

Food sources such as soybeans and fish contain angiotensin I converting enzyme (ACE) inhibitory peptides with antihypertensive properties. Methionine-tyrosine (Met-Tyr) is an ACE inhibitory dipeptide derived from sardine muscle. The present study investigates the effect of Met-Tyr on the expression of the antioxidant stress proteins, heme oxygenase-1 (HO-1) and ferritin, in endothelial cells derived from the human umbilical vein and their contribution to the decrease in radical formation that occurs under the influence of this dipeptide. Preincubation of endothelial cells with Met-Tyr (10-300 μmol/L) followed by washout markedly diminished subsequently induced NADPH-mediated radical formation. This indirect protection was associated with a significant increase in protein expression of HO-1 and ferritin and abolished by the HO inhibitor zinc deuteroporphyrin IX 2,4-bis-ethylene glycol (ZnBG). The HO product bilirubin produced antioxidant effects comparable to those of Met-Tyr. Met-Tyr raised HO-1 mRNA levels by enhancing mRNA stability. Antioxidant effects were specific for Met-Tyr and not observed with other methionine-containing dipeptides or ACE inhibitory agents. Our results demonstrate that Met-Tyr protects endothelial cells from oxidative stress via induction of HO-1 and ferritin but independently of its ACE inhibitory properties. This pathway represents a novel, potentially antiatherogenic mechanism of Met-Tyr and dietary proteins releasing Met-Tyr during gastrointestinal digestion.