A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine.
A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine.
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DOI：
10.1167/iovs.11-8632
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发表时间：
2011-11
影响因子：
4.4
通讯作者：
Kazunori Yamamoto;K. Yoon;K. Ueda;M. Hashimoto;J. Sparrow
中科院分区：
文献类型：
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作者：
Kazunori Yamamoto;K. Yoon;K. Ueda;M. Hashimoto;J. Sparrow
目的荧光双维A酸类化合物在视网膜色素上皮（retinal pigment epithelial，RPE）细胞中的积累是两个过程的结果：维生素A醛在感光细胞外节中的随机反应和RPE对废弃的感光细胞外节盘的吞噬作用。双视黄酸的形成在某些形式的视网膜变性中加重。报道了一种新型的双视黄酸荧光团的检测，该荧光团是全反式视黄酸和甘油磷酸乙醇胺的共轭物。方法采用超高效液相色谱-质谱联用、核磁共振和荧光分光光度法对人RPE/脉络膜、Abca 4（ATP结合盒转运体4）缺失突变小鼠眼组织和生物合成反应混合物进行分析。根据分子量（m/z 746）、吸光度（约338，443 nm）和保留时间测定，小鼠眼睛和人RPE/脉络膜中的荧光化合物对应于全反式-视黄醛和甘油磷酸乙醇胺（A2-GPE）之间的反应产物。核磁共振谱与具有甘油磷酸部分的吡啶分子一致。A2-GPE的最大发射波长约为610 nm。A2-GPE在小鼠眼睛中随着年龄的增长而积累，并且在隐性Stargardt病模型Abca 4（-/-）小鼠中更丰富。结论：迄今为止，已经分离和鉴定了几种RPE脂褐素的双维甲酸，所有这些的形成都涉及膜磷脂磷脂酰乙醇胺。相反，双维甲酸A2-GPE被检测为通过两个全反式-视黄醛衍生的sn-甘油基-3-磷酸乙醇胺（GPE）。A2-GPE的途径可能会形成的条件下增加的可用性的全反式-视网膜，例如在Abca 4（-/-）小鼠，进行了讨论。
PURPOSE Fluorescent bisretinoid compounds accumulate in retinal pigment epithelial (RPE) cells as a consequence of two processes: random reactions of vitamin A aldehyde in photoreceptor cell outer segments, and phagocytosis of discarded photoreceptor outer segment discs by RPE. The formation of bisretinoid is accentuated in some forms of retinal degeneration. The detection of a novel bisretinoid fluorophore that is a conjugate of all-trans-retinal and glycerophosphoethanolamine is reported. METHODS Human RPE/choroid, eyes harvested from Abca4 (ATP-binding cassette transporter 4) null mutant mice, and biosynthetic reaction mixtures were analyzed by ultra performance liquid chromatography coupled to mass spectrometry and by nuclear magnetic resonance spectra and spectrofluorometry. RESULTS A fluorescent compound in mouse eyes and in human RPE/choroid corresponded to the product of the reaction between all-trans-retinal and glycerophosphoethanolamine (A2-GPE), as determined on the basis of molecular weight (m/z 746), absorbance (approximately 338,443 nm), and retention time. Nuclear magnetic resonance spectra were consistent with a pyridinium molecule with a glycerophosphate moiety. The emission maximum of A2-GPE was approximately 610 nm. A2-GPE accumulated with age in mouse eyes and was more abundant in Abca4(-/-) mice, a model of recessive Stargardt disease. CONCLUSIONS To date, several bisretinoids of RPE lipofuscin have been isolated and characterized, and for all of these, formation involves the membrane phospholipid phosphatidylethanolamine. Conversely, the bisretinoid A2-GPE is detected as sn-glycero-3-phosphoethanolamine (GPE) derivatized by two all-trans-retinal. The pathways by which A2-GPE may form under conditions of increased availability of all-trans-retinal, for instance in the Abca4(-/-) mouse, are discussed.