Hepatic-Specific Decrease in the Expression of Selenoenzymes and Factors Essential for Selenium Processing After Endotoxemia.
Hepatic-Specific Decrease in the Expression of Selenoenzymes and Factors Essential for Selenium Processing After Endotoxemia.
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DOI：
10.3389/fimmu.2020.595282
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发表时间：
2020
影响因子：
7.3
通讯作者：
Wright CJ
中科院分区：
文献类型：
--
作者：
Sherlock LG;Sjostrom K;Sian L;Delaney C;Tipple TE;Krebs NF;Nozik-Grayck E;Wright CJ
在急性炎症状态和脓毒症期间，循环中的硒 (Se) 水平降低，并且与发病率和死亡率呈负相关。需要更具体地了解硒蛋白和硒加工在损伤过程中受到损害的位置。我们研究了先天免疫激活后多个器官中硒酶和硒加工机制对全身脂多糖（LPS）的急性信号反应。野生型 (WT) 成年雄性 C57/B6 小鼠暴露于 LPS（5 mg/kg，腹膜内）。从对照小鼠以及 LPS 后 2、4、8 和 24 小时收集血液、肝脏、肺、肾脏和脾脏。通过 ICP-MS 测定血浆 Se 浓度。评估肝脏、肺、肾和脾脏中处理硒所需的硒酶和蛋白质的 mRNA 和蛋白质含量。内毒素血症 8 小时后，硒和硒转运蛋白 SELENOP 的血浆水平显着降低。与这个时间一致的是，包括SELENOP、谷胱甘肽过氧化物酶1和4在内的几种肝硒酶的转录和蛋白质含量显着降低。此外，硒加工所需因子的肝转录和蛋白质含量显着降低，包括硒磷酸合成酶 2 (Sps2)、磷酸丝酰 tRNA 激酶 (Pstk)、硒代半胱氨酸合成酶 (SepsecS) 和硒代半胱氨酸裂解酶 (Scly)。在分离的肝细胞中观察到 LPS 诱导的这些关键硒加工酶的显着下调。与肝脏中观察到的急性和动态变化相反，肺、肾或脾中的硒酶没有减少。内毒素血症后肝脏硒酶的产生和硒加工因子减少。这在时间上与循环硒减少有关。与肝脏中硒加工调节的这些积极变化相反，肺、肾或脾中的硒酶并未减少。这些发现强调需要进一步研究先天免疫挑战对肝脏中硒加工的影响以及先天免疫挑战期间靶向治疗性硒替代策略的影响。
Selenium (Se) levels decrease in the circulation during acute inflammatory states and sepsis, and are inversely associated with morbidity and mortality. A more specific understanding of where selenoproteins and Se processing are compromised during insult is needed. We investigated the acute signaling response in selenoenzymes and Se processing machinery in multiple organs after innate immune activation in response to systemic lipopolysaccharide (LPS). Wild type (WT) adult male C57/B6 mice were exposed to LPS (5 mg/kg, intraperitoneal). Blood, liver, lung, kidney and spleen were collected from control mice as well as 2, 4, 8, and 24 h after LPS. Plasma Se concentration was determined by ICP-MS. Liver, lung, kidney and spleen were evaluated for mRNA and protein content of selenoenzymes and proteins required to process Se. After 8 h of endotoxemia, plasma levels of Se and the Se transporter protein, SELENOP were significantly decreased. Consistent with this timing, the transcription and protein content of several hepatic selenoenzymes, including SELENOP, glutathione peroxidase 1 and 4 were significantly decreased. Furthermore, hepatic transcription and protein content of factors required for the Se processing, including selenophosphate synthetase 2 (Sps2), phosphoseryl tRNA kinase (Pstk), selenocysteine synthase (SepsecS), and selenocysteine lyase (Scly) were significantly decreased. Significant LPS-induced downregulation of these key selenium processing enzymes was observed in isolated hepatocytes. In contrast to the acute and dynamic changes observed in the liver, selenoenzymes did not decrease in the lung, kidney or spleen. Hepatic selenoenzyme production and Se processing factors decreased after endotoxemia. This was temporally associated with decreased circulating Se. In contrast to these active changes in the regulation of Se processing in the liver, selenoenzymes did not decrease in the lung, kidney or spleen. These findings highlight the need to further study the impact of innate immune challenges on Se processing in the liver and the impact of targeted therapeutic Se replacement strategies during innate immune challenge.
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影响因子：
3.7
作者：
Guo, Anne;Srinath, Jyotsna;Chouker, Alexander
通讯作者：
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影响因子：
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10.1016/j.jtemb.2019.126437
发表时间：
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