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标题：The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases
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作者：Yanping Xu ; Szilvia Szép ; Zhe Lu 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：48
页码：20515-20519
DOI：10.1073/pnas.0911412106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cystic fibrosis (CF) is a pleiotropic disease, originating from mutations in the CF transmembrane conductance regulator (CFTR). Lung injuries inflicted by recurring infection and excessive inflammation cause {approx}90% of the morbidity and mortality of CF patients. It remains unclear how CFTR mutations lead to lung illness. Although commonly known as a Cl- channel, CFTR also conducts thiocyanate (SCN-) ions, important because, in several ways, they can limit potentially harmful accumulations of hydrogen peroxide (H2O2) and hypochlorite (OCl-). First, lactoperoxidase (LPO) in the airways catalyzes oxidation of SCN- to tissue-innocuous hypothiocyanite (OSCN-), while consuming H2O2. Second, SCN- even at low concentrations competes effectively with Cl- for myeloperoxidase (MPO) (which is released by white blood cells), thus limiting OCl- production by the enzyme. Third, SCN- can rapidly reduce OCl- without catalysis. Here, we show that SCN- and LPO protect a lung cell line from injuries caused by H2O2; and that SCN- protects from OCl- made by MPO. Of relevance to inflammation in other diseases, we find that in three other tested cell types (arterial endothelial cells, a neuronal cell line, and a pancreatic {beta} cell line) SCN- at concentrations of [≥]100 {micro}M greatly attenuates the cytotoxicity of MPO. Humans naturally derive SCN- from edible plants, and plasma SCN- levels of the general population vary from 10 to 140 {micro}M. Our findings raise the possibility that insufficient levels of antioxidant SCN- provide inadequate protection from OCl-, thus worsening inflammatory diseases, and predisposing humans to diseases linked to MPO activity, including atherosclerosis, neurodegeneration, and certain cancers.
关键词：hydrogen peroxide ; hypochlorite ; hypothiocyanite ; lactoperoxidase ; myeloperoxidase