Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice.
Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice.
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DOI：
10.1053/j.gastro.2015.01.045
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发表时间：
2015-05
期刊：
影响因子：
29.4
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Tsuchiya H;da Costa KA;Lee S;Renga B;Jaeschke H;Yang Z;Orena SJ;Goedken MJ;Zhang Y;Kong B;Lebofsky M;Rudraiah S;Smalling R;Guo G;Fiorucci S;Zeisel SH;Wang L
高同型半胱氨酸血症常与肝脏和代谢性疾病有关。我们研究了核受体介导的振荡控制同型半胱氨酸稳态小鼠。我们研究了Nr 0 b 2（称为SHP-无效小鼠）Bhmt或两种基因（BHMT-无效/SHP-无效小鼠）中的破坏的小鼠，沿着这些基因的野生型拷贝的小鼠（对照）。通过给小鼠喂食酒精（NIAAA狂欢模型）或食物沿着含有0.18%DL-同型半胱氨酸的水来诱导高同型半胱氨酸血症。将一些小鼠置于含有胆酸（1%）或消胆胺（2%）或高脂肪饮食（60%）的饮食中。在24小时光-暗周期内收集血清和肝脏，并通过RNA-seq、代谢组学和定量PCR、免疫印迹和染色质免疫沉淀测定进行分析。与对照组小鼠相比，SHP基因缺失小鼠调节同型半胱氨酸代谢的基因表达时间发生了改变。SHP缺失小鼠和对照小鼠之间S-腺苷甲硫氨酸、甜菜碱、胆碱、磷酸胆碱、糖磷胆碱、胱硫醚、半胱氨酸、硫化氢、二硫代谷胱甘肽和谷胱甘肽的振荡产生不同。SHP通过FOXA 1抑制Bhmt和Cth的转录激活。当小鼠喂食胆酸时，Bhmt和Cth的表达降低，但当它们被放置在含有消胆胺或高脂肪含量的饮食中时，Bhmt和Cth的表达增加。饮食中含有乙醇或同型半胱氨酸诱导高同型半胱氨酸血症和葡萄糖耐受不良的控制，但不是SHP-null小鼠。在喂食对照液体的BHMT无效和BHMT无效/SHP无效小鼠中，在肝脏中观察到脂质空泡。在BHMT-null和BHMT-null/SHP-null小鼠中，乙醇喂养最大程度地诱导大泡脂质空泡的积累。小鼠Shp的破坏改变了调节同型半胱氨酸代谢和肝脏对乙醇和同型半胱氨酸反应的基因表达的时间。SHP通过FOXA 1抑制Bhmt和Cth的转录激活。
Hyperhomocysteinemia is often associated with liver and metabolic diseases. We studied nuclear receptors that mediate oscillatory control of homocysteine homeostasis in mice. We studied mice with disruptions in Nr0b2 (called SHP-null mice) Bhmt, or both genes (BHMT-null/SHP-null mice), along with mice with wild-type copies of these genes (controls). Hyperhomocysteinemia was induced by feeding mice alcohol (the NIAAA binge model) or chow diets along with water containing 0.18% DL-homocysteine. Some mice were placed on diets containing cholic acid (1%) or cholestyramine (2%), or high-fat diets (60%). Serum and livers were collected over a 24 hr light–dark cycle and analyzed by RNA-seq, metabolomic, and quantitative PCR, immunoblot, and chromatin immunoprecipitation assays. SHP-null mice had altered timing in expression of genes that regulate homocysteine metabolism, compared with control mice. Oscillatory production of S-adenosylmethionine, betaine, choline, phosphocholine, glyceophosphocholine, cystathionine, cysteine, hydrogen sulfide, glutathione disulfide, and glutathione, differed between SHP-null mice and control mice. SHP inhibited transcriptional activation of Bhmt and Cth by FOXA1. Expression of Bhmt and Cth was decreased when mice were fed cholic acid but increased when they were placed on diets containing cholestyramine or high-fat content. Diets containing ethanol or homocysteine induced hyperhomocysteinemia and glucose intolerance in control but not SHP-null mice. In BHMT-null and BHMT-null/SHP-null mice fed a control liquid, lipid vacuoles were observed in livers. Ethanol feeding induced accumulation of macrovesicular lipid vacuoles to the greatest extent in BHMT-null and BHMT-null/SHP-null mice. Disruption of Shp in mice alters timing of expression of genes that regulate homocysteine metabolism and the liver responses to ethanol and homocysteine. SHP inhibits the transcriptional activation of Bhmt and Cth by FOXA1.
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影响因子：
13.5
作者：
Kong, Bo;Wang, Li;Guo, Grace L.
通讯作者：
Guo, Grace L.
DOI：
10.2174/1568016054368197
发表时间：
2005-07-01
期刊：
Current Medicinal Chemistry - Cardiovascular & Hematological Agents
影响因子：
--
作者：
Avila, M. A.;Berasain, C.;Corrales, F. J.
通讯作者：
Corrales, F. J.
DOI：
10.1111/j.1530-0277.1993.tb00820.x
发表时间：
1993-06-01
影响因子：
3.2
作者：
HULTBERG, B;BERGLUND, M;FRANK, A
通讯作者：
FRANK, A
影响因子：
3.7
作者：
Dahlhoff C;Desmarchelier C;Sailer M;Fürst RW;Haag A;Ulbrich SE;Hummel B;Obeid R;Geisel J;Bader BL;Daniel H
通讯作者：
Daniel H
FXR 敲除小鼠肝脏中 STAT3 激活的机制。
DOI：
10.1152/ajpgi.00155.2013
发表时间：
2013-12-01
影响因子：
4.5
作者：
Li, Guodong;Zhu, Yan;Guo, Grace L.
通讯作者：
Guo, Grace L.