Umeno Aya, Morita Mayuko, Yoshida Yasukazu, Naito Yuji, Niki Etsuo
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.
Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Gastrointestinal Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Arch Biochem Biophys. 2017 Dec 1;635:96-101. doi: 10.1016/j.abb.2017.10.023. Epub 2017 Oct 31.
Free and ester forms of unsaturated fatty acids and cholesterol are oxidized in vivo by multiple oxidants to give diverse products. Some lipid oxidation is mediated by enzymes to selectively give specific products, while others proceed randomly to produce mixtures of many kinds of regioisomers and stereoisomers. The efficacy of antioxidants against lipid oxidation depends on the nature of the oxidants and therefore the identification of oxidant is important for understanding the roles and effects of lipid oxidation and antioxidants in vivo. In the present study, the isomer distribution of hydro(pero)xyoctadecadienoates (H(p)ODEs) and hydro(pero)xyeicosatetraenoates (H(p)ETEs), the most abundant lipid oxidation products found in human plasma, produced in the oxidation of plasma by peroxyl radicals, peroxynitrite, hypochlorite, 15-lipoxygenase, and singlet oxygen were examined. It was shown that 9- and 13-(E,E)-HODEs, 13(S)-(Z,E)-HODE, and 10- and 12-(Z,E)-HODEs were specific lipid oxidation products by free radical, 15-lipoxygenase, and singlet oxygen, respectively. The isomer distribution of HODEs produced by peroxynitrite was similar to that by peroxyl radical, suggesting that the peroxynitrite mediated lipid oxidation proceeds by free radical mechanisms. The production of HODEs and HETEs by hypochlorite was very small. HODEs may be a better biomarker than HETEs since linoleates are oxidized by simpler mechanisms than arachidonates and all the HODEs isomers can be quantified more easily. These products may be used as specific biomarkers for the identification of responsible oxidants and for the assessment of oxidant-specific lipid oxidation levels and effects of antioxidants in vivo.
不饱和脂肪酸和胆固醇的游离形式及酯形式在体内会被多种氧化剂氧化，生成多种产物。一些脂质氧化由酶介导，选择性地生成特定产物，而另一些则随机进行，产生多种区域异构体和立体异构体的混合物。抗氧化剂对脂质氧化的功效取决于氧化剂的性质，因此确定氧化剂对于理解脂质氧化及抗氧化剂在体内的作用和影响很重要。在本研究中，检测了血浆中最丰富的脂质氧化产物——氢（过氧）十八碳二烯酸酯（H(p)ODEs）和氢（过氧）二十碳四烯酸酯（H(p)ETEs）在过氧自由基、过氧亚硝酸盐、次氯酸盐、15-脂氧合酶和单线态氧氧化血浆过程中产生的异构体分布。结果表明，9-和13-(E,E)-HODEs、13(S)-(Z,E)-HODE以及10-和12-(Z,E)-HODEs分别是自由基、15-脂氧合酶和单线态氧作用下特定的脂质氧化产物。过氧亚硝酸盐产生的HODEs异构体分布与过氧自由基产生的相似，这表明过氧亚硝酸盐介导的脂质氧化是通过自由基机制进行的。次氯酸盐产生的HODEs和HETEs非常少。由于亚油酸酯比花生四烯酸酯的氧化机制更简单，且所有HODEs异构体都更容易定量，因此HODEs可能比HETEs是更好的生物标志物。这些产物可作为特定的生物标志物，用于识别相关氧化剂，评估氧化剂特异性脂质氧化水平以及体内抗氧化剂的作用。
