S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD.
S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD.
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S-腺苷甲硫氨酸通过 NAFLD 中 HuR 的甲基化上调血管紧张素受体结合蛋白 ATRAP
DOI：
10.1038/s41419-021-03591-1
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发表时间：
2021-03-22
影响因子：
9
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Guo T;Dai Z;You K;Battaglia-Hsu SF;Feng J;Wang F;Li B;Yang J;Li Z
非酒精性脂肪性肝病（NAFLD）已在全球范围内出现，并与炎症信号相关。尽管NAFLD已经引起了相当大的关注并进行了广泛的研究，但其潜在的机制仍然不清楚。近年来研究表明，血管紧张素II（AngII）通过其主要受体1型受体（AT 1 R）介导脂质代谢紊乱和胰岛素抵抗，在促进NAFLD进展中发挥重要作用。在此，我们探讨了补充S-腺苷甲硫氨酸（SAM），这是在哺乳动物细胞中的主要生物甲基供体，在调节AT 1 R相关蛋白（ATRAP），这是AT 1 R的负调节。我们发现SAM在NAFLD中被耗尽，并且SAM补充改善了脂肪变性。此外，在高脂饮食喂养的C57 BL/6大鼠和油酸（OA）处理的L02细胞中，ATRAP表达在较低SAM浓度下下调。从机制上讲，我们发现人抗原R（HuR）的亚细胞定位是由蛋白质甲基化修饰引起的SAM浓度决定的。此外，HuR被证明直接结合ATRAP mRNA并控制其核质穿梭。因此，SAM被认为是通过维持其mRNA从细胞核的输出来上调ATRAP蛋白的表达。总之，我们的研究结果表明，SAM可以积极调节NAFLD中的ATRAP，并可能对NAFLD的治疗有各种潜在的益处。
Nonalcoholic fatty liver disease (NAFLD) has emerged globally and is associated with inflammatory signaling. The underlying mechanisms remain poorly delineated, although NAFLD has attracted considerable attention and been extensively investigated. Recent publications have determined that angiotensin II (Ang II) plays an important role in stimulating NAFLD progression by causing lipid metabolism disorder and insulin resistance through its main receptor, Ang II type 1 receptor (AT1R). Herein, we explored the effect of supplementary S-adenosylmethionine (SAM), which is the main biological methyl donor in mammalian cells, in regulating AT1R-associated protein (ATRAP), which is the negative regulator of AT1R. We found that SAM was depleted in NAFLD and that SAM supplementation ameliorated steatosis. In addition, in both high-fat diet-fed C57BL/6 rats and L02 cells treated with oleic acid (OA), ATRAP expression was downregulated at lower SAM concentrations. Mechanistically, we found that the subcellular localization of human antigen R (HuR) was determined by the SAM concentration due to protein methylation modification. Moreover, HuR was demonstrated to directly bind ATRAP mRNA and control its nucleocytoplasmic shuttling. Thus, SAM was suggested to upregulate ATRAP protein expression by maintaining the export of its mRNA from the nucleus. Taken together, our findings suggest that SAM can positively regulate ATRAP in NAFLD and may have various potential benefits for the treatment of NAFLD.
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DOI：
10.5114/ceji.2018.77395
发表时间：
2018
期刊：
Central-European journal of immunology
影响因子：
--
作者：
Kosmalski M;Mokros Ł;Kuna P;Witusik A;Pietras T
通讯作者：
Pietras T
影响因子：
3.4
作者：
Huang, Haiyang;Zhou, Jie;Hu, Yunwei
通讯作者：
Hu, Yunwei
影响因子：
10.5
作者：
Kim, Hyeon Ho;Abdelmohsen, Kotb;Gorospe, Myriam
通讯作者：
Gorospe, Myriam
DOI：
10.1002/wrna.1372
发表时间：
2017-01
期刊：
Wiley interdisciplinary reviews. RNA
影响因子：
--
作者：
Grammatikakis I;Abdelmohsen K;Gorospe M
通讯作者：
Gorospe M
影响因子：
16
作者：
Bedford, Mark T.;Clarke, Steven G.
通讯作者：
Clarke, Steven G.