Method for Structural Determination of Lipid-Derived Radicals
Method for Structural Determination of Lipid-Derived Radicals
复制标题
DOI：
10.1021/acs.analchem.0c00053
复制
发表时间：
2020-05-19
影响因子：
7.4
通讯作者：
Yamada, Ken-ichi
中科院分区：
文献类型：
--
作者：
Matsuoka, Yuta;Izumi, Yoshihiro;Yamada, Ken-ichi
各种氧化脂质分子负责炎症和细胞死亡，包括铁下垂。脂质自由基是这些氧化脂质的来源，这些氧化脂质是脂质过氧化链式反应中最初的关键分子。然而，由于它们极高的反应性和很短的半衰期，目前还没有成熟的检测技术。在这里，我们提出了一种结合荧光探针的高效液相色谱-高分辨率串联质谱学系统，作为脂类自由基的结构分析方法。我们从五种多不饱和脂肪酸中检测到132个脂类自由基，其中包括111个新物种。此外，还建立了一个数据库，可以利用自由基结构确定初始脂肪酸。此外，在致癌物诱导的小鼠肝癌模型中，鉴定出12种内源性脂质衍生自由基。因此，该方法及其相应的数据库将为研究脂质过氧化的潜在机制提供新的见解，包括相关的炎症和铁下垂。
Diversified oxidized-lipid molecules are responsible for inflammation and cell death, including ferroptosis. Lipid radicals are the source of these oxidized lipids, which are the initial key molecules in the lipid peroxidation chain reaction. However, owing to their extremely high reactivity and short half-life, an established detection technique is not available. Here, we propose a high-performance liquid chromatography fluorometry and high-resolution tandem mass spectrometry system combined with a fluorescent probe as a structural analysis method for lipid-derived radicals. We detected 132 lipid-derived radicals, including 111 new species, from five polyunsaturated fatty acids. In addition, a database was constructed for which the initial fatty acid could be determined using the radical structure. Further, 12 endogenous lipid-derived radicals were identified in carcinogen-induced liver cancer mouse models. Therefore, this method and its corresponding database will provide novel insights into mechanisms underlying the lipid peroxidation, including the associated inflammation and ferroptosis.