4-羟基-2-壬烯醛和4-氧代-2-壬烯醛代谢产物的硫醇尿酸共轭物是氧化应激的体内标志物。
Mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites are in vivo markers of oxidative stress.
作者信息
Kuiper Heather C, Miranda Cristobal L, Sowell John D, Stevens Jan F
机构信息
Department of Pharmaceutical Sciences and the Linus Pauling Institute, Oregon State University, Corvallis Oregon 97331, USA.
出版信息
J Biol Chem. 2008 Jun 20;283(25):17131-8. doi: 10.1074/jbc.M802797200. Epub 2008 Apr 27.
Abstract
Oxidative stress-induced lipid peroxidation leads to the formation of cytotoxic and genotoxic 2-alkenals, such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). Lipid-derived reactive aldehydes are subject to phase-2 metabolism and are predominantly found as mercapturic acid (MA) conjugates in urine. This study shows evidence for the in vivo formation of ONE and its phase-1 metabolites, 4-oxo-2-nonen-1-ol (ONO) and 4-oxo-2-nonenoic acid (ONA). We have detected the MA conjugates of HNE, 1,4-dihydroxy-2-nonene (DHN), 4-hydroxy-2-nonenoic acid (HNA), the lactone of HNA, ONE, ONO, and ONA in rat urine by liquid chromatography-tandem mass spectrometry comparison with synthetic standards prepared in our laboratory. CCl(4) treatment of rats, a widely accepted animal model of acute oxidative stress, resulted in a significant increase in the urinary levels of DHN-MA, HNA-MA lactone, ONE-MA, and ONA-MA. Our data suggest that conjugates of HNE and ONE metabolites have value as markers of in vivo oxidative stress and lipid peroxidation.
摘要
氧化应激诱导的脂质过氧化导致细胞毒性和基因毒性2-烯醛的形成，如4-羟基-2-壬烯醛（HNE）和4-氧代-2-壬烯醛（ONE）。脂质衍生的反应性醛会经历二期代谢，并且在尿液中主要以硫醚氨酸（MA）共轭物的形式存在。本研究显示了ONE及其一期代谢产物4-氧代-2-壬烯-1-醇（ONO）和4-氧代-2-壬烯酸（ONA）在体内形成的证据。我们通过液相色谱-串联质谱法与我们实验室制备的合成标准品进行比较，在大鼠尿液中检测到了HNE、1,4-二羟基-2-壬烯（DHN）、4-羟基-2-壬烯酸（HNA）、HNA的内酯、ONE、ONO和ONA的MA共轭物。用四氯化碳（CCl₄）处理大鼠（一种广泛接受的急性氧化应激动物模型），导致尿液中DHN-MA、HNA-MA内酯、ONE-MA和ONA-MA的水平显著增加。我们的数据表明，HNE和ONE代谢产物的共轭物作为体内氧化应激和脂质过氧化的标志物具有价值。
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