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首页> 外文期刊>Biochemistry >Identification of StARD3 as a Lutein-Binding Protein in the Macula of the Primate Retina
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Identification of StARD3 as a Lutein-Binding Protein in the Macula of the Primate Retina

机译：灵长类动物视网膜黄斑中作为叶黄素结合蛋白的StARD3的鉴定

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Lutein, zeaxanthin, and their metabolites are the xanthophyll carotenoids that form the macular pigment of the human retina. Epidemiological evidence suggests that high levels of these carotenoids in the diet, serum, and macula are associated with a decreased risk of age-related macular degeneration (AMD), and the AREDS2 study is prospectively testing this hypothesis. Understanding the biochemical mechanisms underlying the selective uptakes of lutein and zeaxanthin into the human macula may provide important insights into the physiology of the human macula in health and disease. GSTP1 is the macular zeaxanthin-binding protein, but the identity of the human macular lutein-binding protein has remained elusive. Prior identification of the silkworm lutein-binding protein (CBP) as a member of the steroidogenic acute regulatory domain (StARD) protein family and selective labeling of monkey photoreceptor inner segments with an anti-CBP antibody provided an important clue for identifying the primate retina lutein-binding protein. The homology of CBP with all 15 human StARD proteins was analyzed using database searches, Western blotting, and immunohistochemistry, and we here provide evidence to identify StARD3 (also known as MLN64) as a human retinal lutein-binding protein. Antibody to StARD3, N-62 StAR, localizes to all neurons of monkey macular retina and especially cone inner segments and axons, but does not colocalize with the Muller cell marker, glutamine synthetase. Further, recombinant StARD3 selectively binds lutein with high affinity (K-D = 0.45 mu M) when assessed by surface plasmon resonance (SPR) binding assays. Our results demonstrate previously unrecognized, specific interactions of StARD3 with lutein and provide novel avenues for exploring its roles in human macular physiology and disease.
机译：叶黄素，玉米黄质及其代谢产物是形成人视网膜黄斑色素的叶黄素类胡萝卜素。流行病学证据表明，饮食，血清和黄斑中这些类胡萝卜素的高水平与年龄相关性黄斑变性（AMD）的风险降低有关，而AREDS2研究正对该假设进行前瞻性检验。了解叶黄素和玉米黄质选择性摄取到人类黄斑中的潜在生化机制可能为人类黄斑在健康和疾病中的生理学提供重要见解。 GSTP1是黄斑玉米黄质结合蛋白，但人黄斑叶黄素结合蛋白的身份仍然难以捉摸。家蚕叶黄素结合蛋白（CBP）作为类固醇生成急性调节域（StARD）蛋白家族成员的事先鉴定以及用抗CBP抗体选择性标记猴感光体内部片段为鉴定灵长类视网膜叶黄素提供了重要线索结合蛋白。使用数据库搜索，蛋白质印迹和免疫组织化学分析了CBP与所有15种人类StARD蛋白的同源性，我们在此提供证据来鉴定StARD3（也称为MLN64）为人视网膜叶黄素结合蛋白。 StARD3的抗体N-62 StAR定位于猴子黄斑视网膜的所有神经元，尤其是锥体内部节段和轴突，但不与Muller细胞标记物谷氨酰胺合成酶共定位。此外，当通过表面等离振子共振（SPR）结合测定评估时，重组StARD3以高亲和力（K-D = 0.45μM）选择性结合叶黄素。我们的结果证明了StARD3与叶黄素以前无法识别的特异性相互作用，并为探索其在人黄斑生理和疾病中的作用提供了新途径。

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