Biliverdin regulates NR2E3 and zebrafish retinal photoreceptor development.
Biliverdin regulates NR2E3 and zebrafish retinal photoreceptor development.
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Biliverdin 调节 NR2E3 和斑马鱼视网膜感光细胞的发育。
DOI：
10.1038/s41598-022-11502-3
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发表时间：
2022-05-04
影响因子：
4.6
通讯作者：
Lee, Young-Sam
中科院分区：
文献类型：
--
作者：
Connor, Blaine;Titialii-Torres, Kayla;Rockenhaus, Abigail E.;Passamonte, Samuel;Morris, Ann C.;Lee, Young-Sam
NR2E3是一种孤儿核受体，其功能丧失导致视网膜感光细胞发育和变性异常。然而，尽管许多核受体通过小分子配体的结合来调节，但尚未鉴定出调节NR2E3的生物小分子配体。内源性NR2E3配体的鉴定可能揭示了一种以前未被认识到的有助于视网膜发育和维持的成分。在这里，我们报告，胆绿素，一个保守的绿色色素血红素catalysts，调节NR2E3，是必要的斑马鱼视网膜感光细胞的发展。从视网膜提取物中提取的胆绿素特异性结合NR2E3的配体结合域，并诱导NR2E3依赖性报告基因的表达。抑制胆绿素的合成减少了斑马鱼幼虫的感光细胞数量，这种表型被外源性提供的胆绿素缓解。因此，胆绿素是NR2E3的内源性小分子配体，也是感光细胞正常发育所必需的组分。这一结果表明，血红素代谢在视网膜感光细胞发育的调节中可能发挥作用。
NR2E3 is an orphan nuclear receptor whose loss-of-function causes abnormal retinal photoreceptor development and degeneration. However, despite that many nuclear receptors are regulated by binding of small molecule ligands, biological small molecule ligands regulating NR2E3 have not been identified. Identification of an endogenous NR2E3 ligand might reveal a previously unrecognized component contributing to retinal development and maintenance. Here we report that biliverdin, a conserved green pigment from heme catabolism, regulates NR2E3 and is necessary for zebrafish retinal photoreceptor development. Biliverdin from retinal extracts specifically bound to NR2E3’s ligand-binding domain and induced NR2E3-dependent reporter gene expression. Inhibition of biliverdin synthesis decreased photoreceptor cell populations in zebrafish larvae, and this phenotype was alleviated by exogenously supplied biliverdin. Thus, biliverdin is an endogenous small molecule ligand for NR2E3 and a component necessary for the proper development of photoreceptor cells. This result suggests a possible role of heme metabolism in the regulation of retinal photoreceptor cell development.
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影响因子：
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作者：
Choudhary M;Malek G
通讯作者：
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影响因子：
3.5
作者：
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DOI：
10.1124/jpet.106.102699
发表时间：
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影响因子：
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作者：
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通讯作者：
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