Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement
Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement
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DOI：
10.1002/1521-3773(20020301)41:5
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发表时间：
2002-01-01
影响因子：
16.6
通讯作者：
Nakanishi, K
中科院分区：
文献类型：
--
作者：
Ben-Shabat, S;Itagaki, Y;Nakanishi, K
在视网膜色素上皮（retinal pigment epithelium，RPE）细胞中积累的脂褐素可能在RPE细胞的恶化和死亡中起作用，这是萎缩性年龄相关性黄斑变性（aged related macular degeneration，AMD）的典型特征。在人类视网膜色素上皮细胞中，这种老化色素的沉积在20岁时已经很明显，[1]虽然它继续增加，直到大约70岁，此后它会下降。[2±4] RPE脂褐素的主要疏水荧光团是吡啶双维甲酸A2 E（1）（图1，左上）和iso-A2 E，其13-Z光异构体。[5±8] A2 E是由A2-PE水解裂解形成的，A2-PE是由两个分子的全反式视黄醇和磷脂酰乙醇胺（PE）反应产生的前体。[9]最近已经表明，A2 E通过培养的RPE的积累赋予对光诱导的损伤的敏感性。[10具体地，发现光谱的蓝色区域诱导含A2 E的细胞的凋亡性死亡，具有反映A2 E的激发光谱的波长依赖性。[11由蓝光照射的载有A2 E的RPE细胞经历细胞凋亡的倾向与动物模型中RPE细胞对蓝光损伤的已知易感性一致。[13此外，A2 E作为光损伤引发剂的能力可能与将晚期萎缩性AMD的发病率与蓝光暴露（特别是在晚年）联系起来的研究相关。[16]为了研究A2 E的蓝光诱导的修饰，将其在含有0.1%DMSO的磷酸盐缓冲盐水（PBS）（200 μm; 200 μL）中的溶液用于溶解目的，用来自150-W卤钨灯（辐射能0.19 mW mm 2）的蓝光（（430 nm））照射。辐照10 min产生了一系列氧化衍生物，每一种都代表了加成反应。
The lipofuscin that accumulates in retinal pigment epithelium (RPE) cells may play a role in the deterioration and death of RPE cells which is typical of atrophic age-related macular degeneration (AMD). In human RPE cells, the deposition of this aging pigment is already apparent by age 20,[1] and while it continues to increase until approximately age 70, thereafter it declines.[2±4] The major hydrophobic fluorophores of RPE lipofuscin are the pyridinium bisretinoids A2E (1)(Figure 1, top left) and iso-A2E, its 13-Z photo-isomer.[5±8] A2E is formed by hydrolytic cleavage of A2-PE, a precursor generated from the reaction between two molecules of all-trans-retinal and phosphatidylethanolamine (PE).[9] It has recently been shown that the accumulation of A2E by cultured RPE bestows a sensitivity to light-induced damage.[10, 11] Specifically, the blue region of the spectrum was found to induce the apoptotic death of A2E-containing cells, with a wavelength dependency that reflected the excitation spectrum of A2E.[11, 12] The propensity for A2E-laden RPE cells illuminated by blue light to undergo apoptosis is consistent with the known susceptibility of RPE cells to blue light damage in animal models.[13±15] Moreover, the ability of A2E to serve as an initiator of photodamage may be relevant to studies linking the incidence of advanced atrophic AMD with blue light exposure, particularly in later life.[16]To investigate the blue-light-induced modification of A2E, solutions of it in phosphate-buffered saline (PBS)(200 μm; 200 μL) containing 0.1% of DMSO for solubility purposes were irradiated with blue light ((430 Æ 10) nm) delivered from a 150-W tungsten halogen lamp (radiant energy 0.19 mW mmÀ2). Irradiation for 10 min generated a series of oxidative derivatives, each of which represented the addition