L-methionine reduces oxidant stress in endothelial cells: role of heme oxygenase-1, ferritin, and nitric oxide.
The amino acid L-methionine is known to exert antioxidant effects by as yet unidentified mechanisms. In the present study, L-methionine led to a concentration-dependent induction of the antioxidant proteins heme oxygenase-1 (HO-1) and ferritin in cultured endothelial cells (ECV 304). HO-1 protein expression was accompanied by an increased catalytic activity of the enzyme. Long-term pre-incubation of endothelial cells with L-methionine reduced NADPH-mediated radical formation by up to 60%. The antioxidant effect of L-methionine was mimicked by the HO-1 product bilirubin, which suppressed free radical formation almost completely. Reduction of superoxide generation by L-methionine was inhibited in the presence of the nitric oxide (NO) synthase inhibitor L-NMMA, suggesting the involvement of endogenous NO in L-methionine-dependent cytoprotection. These findings demonstrate that L-methionine reduces free radical formation in endothelial cells, possibly through induction of heme oxygenase-1 and ferritin. This novel, indirect antioxidant action might be relevant for the preventive potential of methionine and methionine rich diets under conditions of inflammation and oxidative stress.
Erdmann
Kati
K
Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, 06099 Halle, Saale, Germany.
Grosser
Nina
N
Schroder
Henning
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001663:Bilirubin / Q000494:pharmacology; D002384:Catalysis; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003905:Deuteroporphyrins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005293:Ferritins / Q000096:biosynthesis / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008163:Luminescent Measurements; D008715:Methionine / Q000494:pharmacology*; D009249:NADP / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D003905:Deuteroporphyrins; D016166:Free Radical Scavengers; D005609:Free Radicals; D013481:Superoxides; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009249:NADP; D005293:Ferritins; D008715:Methionine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001663:Bilirubin