Uridine affects liver protein glycosylation, insulin signaling, and heme biosynthesis.
Uridine affects liver protein glycosylation, insulin signaling, and heme biosynthesis.
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尿苷会影响肝蛋白糖基化，胰岛素信号传导和血红素生物合成。
DOI：
10.1371/journal.pone.0099728
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Le TT
中科院分区：
文献类型：
--
作者：
Urasaki Y;Pizzorno G;Le TT
嘌呤和嘧啶是遗传密码的互补碱基。嘌呤及其衍生物在细胞信号转导和能量代谢中的作用是众所周知的。相比之下，嘧啶及其衍生物在细胞功能中的作用仍然知之甚少。在这项研究中，尿苷，嘧啶核苷，在肝脏代谢中的作用在小鼠中进行了检查。我们报告了C57 BL/6 J小鼠短期尿苷给药增加了肝脏蛋白糖基化谱，降低了胰岛素信号蛋白的磷酸化水平，并激活了HRI-eIF-2α-ATF 4血红素缺乏应激反应途径。短期尿苷给药也与肝氯化血红素水平降低和胰岛素耐量试验期间胰岛素刺激的血糖清除能力降低相关。外源尿苷在C57 BL/6 J小鼠中的一些短期效应在转基因UPase 1 −/−小鼠中是保守的，内源尿苷水平长期升高。UPase 1 −/−小鼠表现出肝脏HRI-eIF-2α-ATF 4血红素缺乏应激反应途径的激活。UPase 1 −/−小鼠也表现出胰岛素刺激的血糖清除能力受损。然而，外源尿苷在C57 BL/6 J小鼠中的其他短期效应在UPase 1 −/−小鼠中并不保守。与未处理的对照C57 BL/6 J小鼠相比，UPase 1 −/−小鼠表现出正常的肝脏胰岛素信号蛋白磷酸化水平和增加的肝脏氯化血红素浓度。对比尿苷对肝脏代谢的短期和长期后果表明，尿苷发挥短暂的作用，并激发适应性反应。总之，我们的数据支持嘧啶及其衍生物在调节肝脏代谢中的潜在作用。
Purines and pyrimidines are complementary bases of the genetic code. The roles of purines and their derivatives in cellular signal transduction and energy metabolism are well-known. In contrast, the roles of pyrimidines and their derivatives in cellular function remain poorly understood. In this study, the roles of uridine, a pyrimidine nucleoside, in liver metabolism are examined in mice. We report that short-term uridine administration in C57BL/6J mice increases liver protein glycosylation profiles, reduces phosphorylation level of insulin signaling proteins, and activates the HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. Short-term uridine administration is also associated with reduced liver hemin level and reduced ability for insulin-stimulated blood glucose removal during an insulin tolerance test. Some of the short-term effects of exogenous uridine in C57BL/6J mice are conserved in transgenic UPase1 −/− mice with long-term elevation of endogenous uridine level. UPase1 −/− mice exhibit activation of the liver HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. UPase1 −/− mice also exhibit impaired ability for insulin-stimulated blood glucose removal. However, other short-term effects of exogenous uridine in C57BL/6J mice are not conserved in UPase1 −/− mice. UPase1 −/− mice exhibit normal phosphorylation level of liver insulin signaling proteins and increased liver hemin concentration compared to untreated control C57BL/6J mice. Contrasting short-term and long-term consequences of uridine on liver metabolism suggest that uridine exerts transient effects and elicits adaptive responses. Taken together, our data support potential roles of pyrimidines and their derivatives in the regulation of liver metabolism.
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