L-methionine reduces oxidant stress in endothelial cells:: Role of heme oxygenase-1, ferritin, and nitric oxide
L-methionine reduces oxidant stress in endothelial cells:: Role of heme oxygenase-1, ferritin, and nitric oxide
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DOI：
10.1208/aapsj070118
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发表时间：
2005-01-01
期刊：
影响因子：
4.5
通讯作者：
Schröder, H
中科院分区：
文献类型：
--
作者：
Erdmann, K;Grosser, N;Schröder, H
已知氨基酸L-甲硫氨酸通过尚未鉴定的机制发挥抗氧化作用。在本研究中，L-蛋氨酸导致浓度依赖性诱导的抗氧化蛋白血红素加氧酶-1（HO-1）和铁蛋白在培养的内皮细胞（ECV 304）。HO-1蛋白表达伴随着酶的催化活性增加。内皮细胞与L-甲硫氨酸的长期预孵育可使NADPH介导的自由基形成减少高达60%。L-甲硫氨酸的抗氧化作用被HO-1产物胆红素模仿，其几乎完全抑制自由基的形成。在一氧化氮（NO）合酶抑制剂L-NMMA的存在下，由L-甲硫氨酸的超氧化物生成的减少被抑制，这表明内源性NO参与L-甲硫氨酸依赖的细胞保护。这些发现表明，L-蛋氨酸减少内皮细胞中自由基的形成，可能是通过诱导血红素加氧酶-1和铁蛋白。这种新的间接抗氧化作用可能与甲硫氨酸和富含甲硫氨酸的饮食在炎症和氧化应激条件下的预防潜力有关。
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.