Differential and isomer-specific modulation of vitamin A transport and the catalytic activities of the RBP receptor by retinoids.
Differential and isomer-specific modulation of vitamin A transport and the catalytic activities of the RBP receptor by retinoids.
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DOI：
10.1007/s00232-013-9578-z
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发表时间：
2013-08
影响因子：
2.4
通讯作者：
Sun, Hui
中科院分区：
文献类型：
--
作者：
Kawaguchi, Riki;Zhong, Ming;Kassai, Miki;Ter-Stepanian, Mariam;Sun, Hui
类视黄醇是具有多种生物学功能的维生素A衍生物。天然和人工类视黄醇都已被用作治疗人类疾病的药物，但并非所有类视黄醇的作用机制都已被了解。血浆视黄醇结合蛋白（RBP）是血液中维生素A的主要且特异性的载体。STRA6是RBP的膜受体，介导细胞对维生素A的摄取。类视黄醇或相关化合物对该受体摄取维生素A的活性及其催化活性的影响尚未被充分了解。在这项研究中，我们使用各种类视黄醇剖析了膜受体介导的维生素A摄取机制。我们发现一部分类视黄醇强烈刺激STRA6介导的维生素A从全RBP中释放。STRA6还催化RBP中的视黄醇与某些类视黄醇进行交换。类视黄醇对STRA6的影响具有高度的异构体特异性。这项研究为RBP受体的机制提供了独特的见解，并揭示维生素A转运机制可成为基于类视黄醇的药物的作用靶点。
Retinoids are vitamin A derivatives with diverse biological functions. Both natural and artificial retinoids have been used as therapeutic reagents to treat human diseases, but not all retinoid actions are understood mechanistically. Plasma retinol binding protein (RBP) is the principal and specific carrier of vitamin A in the blood. STRA6 is the membrane receptor for RBP that mediates cellular vitamin A uptake. The effects of retinoids or related compounds on the receptor’s vitamin A uptake activity and its catalytic activities are not well understood. In this study, we dissected the membrane receptor-mediated vitamin A uptake mechanism using various retinoids. We show that a subset of retinoids strongly stimulates STRA6-mediated vitamin A release from holo-RBP. STRA6 also catalyzes the exchange of retinol in RBP with certain retinoids. The effect of retinoids on STRA6 is highly isomer-specific. This study provides unique insights into the RBP receptor’s mechanism and reveals that the vitamin A transport machinery can be a target of retinoid-based drugs.
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影响因子：
56.9
作者：
BLOMHOFF, R;GREEN, MH;NORUM, KR
通讯作者：
NORUM, KR
影响因子：
7.3
作者：
Chivot, M
通讯作者：
Chivot, M
影响因子：
7.5
作者：
LOVE, JM;GUDAS, LJ
通讯作者：
GUDAS, LJ
影响因子：
3
作者：
DOWLING, JE
通讯作者：
DOWLING, JE
影响因子：
2.9
作者：
Kawaguchi, Riki;Yu, Jiarnei;Sun, Hui
通讯作者：
Sun, Hui