Investigation of the Tissue Distribution and Physiological Roles of Indoleamine 2,3-Dioxygenase-2.
Investigation of the Tissue Distribution and Physiological Roles of Indoleamine 2,3-Dioxygenase-2.
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DOI：
10.1177/1178646917735098
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ball HJ
中科院分区：
文献类型：
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作者：
Jusof FF;Bakmiwewa SM;Weiser S;Too LK;Metz R;Prendergast GC;Fraser ST;Hunt NH;Ball HJ
吲哚胺 2,3-双加氧酶-2 (IDO2) 是可催化色氨酸代谢犬尿氨酸途径第一步的 3 种酶之一。在其他 2 种酶中，色氨酸 2,3-双加氧酶在肝脏中高表达，并在色氨酸稳态中发挥作用，而吲哚胺 2,3-双加氧酶-1 (IDO1) 表达由炎症刺激诱导。据报道，吲哚胺 2,3-双加氧酶-2 的表达范围相对较窄，包括在肝、肾、脑和某些免疫细胞类型中，并且在正常生理条件下，它似乎对全身色氨酸分解代谢没有显着贡献。在这里，我们报告了另一种剪接模式的鉴定，包括使用小鼠 Ido1 和 Ido2 基因中保守的另一种第一外显子。这些发现促使我们评估组织中 IDO2 蛋白的表达和酶活性。我们的分析是在 Ido2 +/+ 和 Ido2−/− 小鼠中使用免疫组织化学和色氨酸和犬尿氨酸水平测量进行的，结果表明组织表达模式比之前报道的更加受限。我们发现 IDO2 蛋白在肝脏中表达，分布在核周/核，而不是细胞质。与之前的报道一致，我们发现 Ido2 −/− 小鼠在血浆和肝脏中的色氨酸和犬尿氨酸水平方面与 Ido2+/+ 小鼠表型相似。我们的研究结果表明 IDO2 的特殊功能或调节作用与其特定的亚细胞定位相关。
Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1) expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is reportedly expressed comparatively narrow, including in liver, kidney, brain, and in certain immune cell types, and it does not appear to contribute significantly to systemic tryptophan catabolism under normal physiological conditions. Here, we report the identification of an alternative splicing pattern, including the use of an alternative first exon, that is conserved in the mouse Ido1 and Ido2 genes. These findings prompted us to assess IDO2 protein expression and enzymatic activity in tissues. Our analysis, undertaken in Ido2 +/+ and Ido2−/− mice using immunohistochemistry and measurement of tryptophan and kynurenine levels, suggested an even more restricted pattern of tissue expression than previously reported. We found IDO2 protein to be expressed in the liver with a perinuclear/nuclear, rather than cytoplasmic, distribution. Consistent with earlier reports, we found Ido2 −/− mice to be phenotypically similar to their Ido2+/+ counterparts regarding levels of tryptophan and kynurenine in the plasma and liver. Our findings suggest a specialized function or regulatory role for IDO2 associated with its particular subcellular localization.