S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD

作者全名："Guo, Tao; Dai, Zhe; You, Ke; Battaglia-Hsu, Shyue-Fang; Feng, Juan; Wang, Fengliang; Li, Bao; Yang, Jian; Li, Zhen"

作者地址："[Guo, Tao] Weifang Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Weifang 261053, Peoples R China; [Dai, Zhe] Wuhan Univ, Dept Endocrinol, Zhongnan Hosp, Wuhan 430071, Peoples R China; [You, Ke] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Battaglia-Hsu, Shyue-Fang] Univ Lorraine, Fac Med Nancy, Nutr Genet & Environm Risk Exposure, F-54000 Vandoeuvre Les Nancy, France; [Battaglia-Hsu, Shyue-Fang] Univ Reg Hosp, F-54000 Vandoeuvre Les Nancy, France; [Feng, Juan] Wuhan Univ, Sch Hlth Sci, Wuhan 430072, Peoples R China; [Wang, Fengliang] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Dept Breast Surg, Affiliated Obstet & Gynaecol Hosp, Nanjing 210004, Peoples R China; [Li, Bao] Weifang Peoples Hosp, Dept Urol, Weifang 261000, Shandong, Peoples R China; [Yang, Jian] Huanggang Polytech Coll, Sch Nursing, Huanggang 438002, Peoples R China; [Li, Zhen] Wuhan Univ, Dept Hepatobiliary & Pancreat Surg, Zhongnan Hosp, Wuhan 430071, Peoples R China"

通信作者："Li, Z (corresponding author), Wuhan Univ, Dept Hepatobiliary & Pancreat Surg, Zhongnan Hosp, Wuhan 430071, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000634783900005

JCR分区：Q1

影响因子：9

年份：2021

卷号：12

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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."

基金机构："Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [2042018kf0079]; Hubei Province Natural Science Foundation of ChinaNatural Science Foundation of Hubei Province [2018CFB157]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81800522]; Research start-up funds of Weifang Medical University [04102001]; Natural Science Foundation of Shandong Province, ChinaNatural Science Foundation of Shandong Province [ZR2016HL12]"

基金资助正文："This work was supported by the Fundamental Research Funds for the Central Universities (No. 2042018kf0079), Hubei Province Natural Science Foundation of China (No. 2018CFB157), National Natural Science Foundation of China (No. 81800522), Research start-up funds of Weifang Medical University (No. 04102001), and The Natural Science Foundation of Shandong Province, China (No. ZR2016HL12)."