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Selenium-deficient diet induces necroptosis in the pig brain by activating TNFR1 via mir-29a-3p.
Metallomics ( IF 2.9 ) Pub Date : 2020-05-28 , DOI: 10.1039/d0mt00032a
Jiawen Cui 1 , Honggui Liu , Shiwen Xu
Affiliation  

Selenium (Se) deficiency is one of the crucial factors related to nervous system disease and necroptosis. MicroRNAs (miRNAs) play vital roles in regulating necroptosis. However, the mechanism of Se deficiency-induced necroptosis in the pig brain tissue and the role that miRNAs play in this process are unclear. Therefore, in this study, in vitro and pig models of Se deficiency were replicated, and electron microscopy, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were performed. The results showed that brain cells typically undergo necrotic changes, and that Se deficiency suppresses mir-29a-3p, which increases the levels of TNFRSF1A (TNFR1). Subsequently, a distinct increase in the necroptosis markers (RIPK1, RIPK3, and MLKL) and an evident decrease in caspase 8 was observed. And the expression of 10 selenoproteins was decreased. Moreover, the in vitro experiments showed that the expression of mir-29a-3p decreased as the Se content in the medium decreased and the application of an mir-29a-3p inhibitor increased the number of necrotic cells and the accumulation of ROS, and these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC), respectively. Taken together, we proved that Se deficiency induced necroptosis both in vitro and in vivo through the targeted regulation of TNFR1 by mir-29a-3p in the pig brain.

中文翻译:

缺硒饮食通过 mir-29a-3p 激活 TNFR1 诱导猪脑中的坏死性凋亡。

硒(Se)缺乏是与神经系统疾病和坏死性凋亡相关的关键因素之一。MicroRNAs (miRNAs) 在调节坏死性凋亡中起着至关重要的作用。然而,硒缺乏引起猪脑组织坏死性凋亡的机制以及miRNA在该过程中的作用尚不清楚。因此,在本研究中,体外复制缺硒和猪模型,并进行电子显微镜检查、定量实时聚合酶链反应 (qRT-PCR) 和蛋白质印迹分析。结果表明,脑细胞通常会发生坏死性变化,硒缺乏会抑制 mir-29a-3p,从而增加 TNFRSF1A (TNFR1) 的水平。随后,观察到坏死性凋亡标志物(RIPK1、RIPK3 和 MLKL)的明显增加和半胱天冬酶 8 的明显减少。10种硒蛋白表达降低。此外,体外实验表明,随着培养基中Se含量的降低,mir-29a-3p的表达降低,而mir-29a-3p抑制剂的应用增加了坏死细胞的数量和ROS的积累,这些作用被necrostatin抑制-1 (Nec-1) 和N -乙酰半胱氨酸 (NAC),分别。总之,我们证明了硒缺乏通过 mir-29a-3p 在猪脑中对 TNFR1 的靶向调节在体外体内诱导了坏死性凋亡。
更新日期:2020-05-28
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