Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid

作者: Faten Shaeib , Sana N. Khan , Iyad Ali , Tohid Najafi , Dhiman Maitra

DOI: 10.1371/JOURNAL.PONE.0120737

关键词:

摘要: Myeloperoxidase (MPO) generated hypochlorous acid (HOCl) formed during catalysis is able to destroy the MPO heme moiety through a feedback mechanism, resulting in accumulation of free iron. Here we show that presence melatonin (MLT) can prevent HOCl-mediated destruction using combination UV-visible photometry, hydrogen peroxide (H2O2)-specific electrode, and ferrozine assay techniques. High performance liquid chromatography (HPLC) analysis showed protection was at expense MLT oxidation. The full requires 1:2 H2O2 ratio. Melatonin prevents HOCl–mediated multiple pathways. These include competition with chloride, natural co-substrate; switching activity from two electron oxidation one pathway causing buildup inactive Compound II, its subsequent decay MPO-Fe(III) instead generating HOCl; binding above iron, thereby preventing access catalytic site enzyme; direct scavenging HOCl. Collectively, addition acting as an antioxidant inhibitor, exert protective effect by release iron mediated self-generated Our work may establish mechanistic link which exerts chronic inflammatory diseases elevation.

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