Bisretinoids: More than Meets the Eye.
Bisretinoids: More than Meets the Eye.
复制标题
双维A酸：不仅仅是表面上看到的。
DOI：
10.1007/978-3-030-27378-1_56
复制
发表时间：
2019
影响因子：
--
通讯作者：
Sparrow,JanetR
中科院分区：
文献类型：
--
作者：
Kim,HyeJin;Sparrow,JanetR
双维A类荧光团是视网膜色素上皮(RPE)脂褐素的主要成分，随着年龄的增长而积累，并与视网膜疾病有关。对这些光毒性视黄醛加合物的积累对RPE细胞造成的负担的了解取决于对构成这一荧光团家族的各种双维A酸类物种的鉴定和定量。在这里，我们报告了一种先前未知的荧光双维A酸类化合物，通过UPLC与光电二极管阵列检测、荧光和电喷雾电离质谱仪(UPLC-PDA-FLR-ESI-MS)相耦合(Kim HJ，Sparrow Jr，J Lipid RES 59：1620-1629,2018)。新的双维A酸类化合物为1-十八基-2-赖索-sn-甘油A_2PE(烷基醚A_2PE)。结构归属基于分子量(m/z998)、紫外可见吸收峰(340,440 nm)和保留时间(73分钟)，并通过以全反式视黄醇和甘油磷乙醇胺类似物为原料的仿生合成得到证实。在机理研究中，A2PE被PLA2水解，在酸性条件下裂解纤溶酶原A2PE。UPLC史无前例地在人RPE中检测到双维A酸烷基醚溶解A2PE，但在神经视网膜中没有检测到，表明产生后者的磷脂酶A2活性存在于RPE中。
Bisretinoid fluorophores are the major constituents of the lipofuscin of retinal pigment epithelium (RPE) that accumulates with age and contributes to retina disease. Knowledge of the burden placed on the RPE cell by the accumulation of these phototoxic retinaldehyde-adducts depends on the identification and quantitation of the various bisretinoid species that constitute this family of fluorophores. Here we report a previously unidentified fluorescent bisretinoid by UPLC coupled to photodiode array detection, fluorescence, and electrospray ionization mass spectrometry (UPLC-PDA-FLR-ESI-MS) (Kim HJ, Sparrow JR, J Lipid Res 59:1620-1629, 2018). This novel bisretinoid is 1-octadecyl-2-lyso-sn-glycero A2PE (alkyl ether lysoA2PE). The structural assignment was based on molecular weight (m/z998), UV-visible absorbance maxima (340, 440 nm), and retention time (73 minutes) and was corroborated by biomimetic synthesis using all-trans-retinal and glycerophosphoethanolamine analogues as starting materials. In mechanistic studies, A2PE was hydrolyzed by PLA2, and plasmalogen lysoA2PE was cleaved under acidic conditions. Unprecedented UPLC detection of the bisretinoid alkyl ether lysoA2PE in human RPE but not in neural retina indicates that the phospholipase A2activity that generates the latter bisretinoid resides in RPE.