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L-methionine reduces oxidant stress in endothelial cells: Role of heme oxygenase-1, ferritin, and nitric oxide

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Abstract

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 protein 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 and 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.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, 06099, Halle (Salle), Germany

    Kati Erdmann, Nina Grosser & Henning Schröder

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  1. Kati Erdmann
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  2. Nina Grosser
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  3. Henning Schröder
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Correspondence to Henning Schröder.

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Published: August 29, 2005

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Erdmann, K., Grosser, N. & Schröder, H. L-methionine reduces oxidant stress in endothelial cells: Role of heme oxygenase-1, ferritin, and nitric oxide. AAPS J 7, 18 (2005). https://doi.org/10.1208/aapsj070118

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  • DOI: https://doi.org/10.1208/aapsj070118

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