Hepatic Proteomic Analysis of Selenoprotein T Knockout Mice by TMT: Implications for the Role of Selenoprotein T in Glucose and Lipid Metabolism.
Hepatic Proteomic Analysis of Selenoprotein T Knockout Mice by TMT: Implications for the Role of Selenoprotein T in Glucose and Lipid Metabolism.
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DOI：
10.3390/ijms22168515
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发表时间：
2021-08-07
影响因子：
5.6
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Li K;Feng T;Liu L;Liu H;Huang K;Zhou J
硒蛋白T（Selenoprotein T，SELENOT，SelT）是一种硫氧还蛋白样酶，在内质网中发挥重要的氧化还原酶活性。然而，它的确切功能仍然未知。为了更好地了解SELENOT功能，首次使用CRISPR/Cas9技术构建了常规的整体Selenot敲除（KO）小鼠模型。删除SELENOT可导致雄性不育、体型/体重减小、进食和/或空腹血糖水平降低和空腹血清胰岛素水平降低以及血脂谱改善。采用串联质量标签（TMT）蛋白质组学方法对雄性小鼠肝脏中的差异表达蛋白进行分析，发现KO小鼠肝脏中有60个差异表达蛋白，而94个差异表达蛋白。蛋白质组学结果通过蛋白质印迹法进行验证。肝脏糖原[淀粉]合成酶（Gys 2）的表达升高与KO小鼠的低血糖表型一致。生物信息学分析表明，Selenot-KO诱导的DEPs主要与脂质代谢、肿瘤、过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPAR）信号通路、补体和凝血级联反应以及蛋白质消化吸收有关。总的来说，这些发现提供了一个全面的视角，以了解SELENOT功能和新的见解，在葡萄糖和脂质代谢中的作用，从而提高我们的理解SELENOT功能。
Selenoprotein T (SELENOT, SelT), a thioredoxin-like enzyme, exerts an essential oxidoreductase activity in the endoplasmic reticulum. However, its precise function remains unknown. To gain more understanding of SELENOT function, a conventional global Selenot knockout (KO) mouse model was constructed for the first time using the CRISPR/Cas9 technique. Deletion of SELENOT caused male sterility, reduced size/body weight, lower fed and/or fasting blood glucose levels and lower fasting serum insulin levels, and improved blood lipid profile. Tandem mass tag (TMT) proteomics analysis was conducted to explore the differentially expressed proteins (DEPs) in the liver of male mice, revealing 60 up-regulated and 94 down-regulated DEPs in KO mice. The proteomic results were validated by western blot of three selected DEPs. The elevated expression of Glycogen [starch] synthase, liver (Gys2) is consistent with the hypoglycemic phenotype in KO mice. Furthermore, the bioinformatics analysis showed that Selenot-KO-induced DEPs were mainly related to lipid metabolism, cancer, peroxisome proliferator-activated receptor (PPAR) signaling pathway, complement and coagulation cascades, and protein digestion and absorption. Overall, these findings provide a holistic perspective into SELENOT function and novel insights into the role of SELENOT in glucose and lipid metabolism, and thus, enhance our understanding of SELENOT function.
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影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
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DOI：
10.1016/j.bbamcr.2012.02.018
发表时间：
2012-09
影响因子：
5.1
作者：
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通讯作者：
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