Identification of novel regulatory cholesterol metabolite, 5-cholesten, 3β,25-diol, disulfate.
Identification of novel regulatory cholesterol metabolite, 5-cholesten, 3β,25-diol, disulfate.
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DOI：
10.1371/journal.pone.0103621
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ning Y
中科院分区：
文献类型：
--
作者：
Ren S;Kim JK;Kakiyama G;Rodriguez-Agudo D;Pandak WM;Min HK;Ning Y
氧化甾醇硫酸化在调节脂质代谢和炎症反应中起重要作用。在本研究中，我们报告了一种新的监管硫酸氧化固醇在原代大鼠肝细胞核过表达后的线粒体胆固醇传递蛋白（StarD 1）的基因编码的发现。用重组StarD 1腺病毒感染肝细胞48小时后，通过化学萃取和反相HPLC分离并纯化水溶性氧化固醇产物。串联质谱分析鉴定了氧化甾醇为5-甾烯-3 β，25-二醇，二硫酸酯（25 HCDS），并通过与化学合成的化合物进行比较来确认结构。在NAFLD小鼠模型中，向人THP-1衍生的巨噬细胞或HepG 2细胞施用25 HCDS显著抑制胆固醇合成并显著降低体内脂质水平。RT-PCR结果表明，25 HCDS通过抑制SREBP-1/2活性相关基因ACC、FAS和HMG-CoA还原酶的表达，显著降低SREBP-1/2活性。肝脏组织中的脂质谱分析表明，25 HCDS给药可显著降低胆固醇、游离脂肪酸和甘油三酯，分别降低30%、25%和20%。结果表明，25 HCDS通过阻断SREBP信号通路抑制脂质生物合成。我们的结论是，25 HCDS是一个有效的调节脂质代谢，并提出其生物合成途径。
Oxysterol sulfation plays an important role in regulation of lipid metabolism and inflammatory responses. In the present study, we report the discovery of a novel regulatory sulfated oxysterol in nuclei of primary rat hepatocytes after overexpression of the gene encoding mitochondrial cholesterol delivery protein (StarD1). Forty-eight hours after infection of the hepatocytes with recombinant StarD1 adenovirus, a water-soluble oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Tandem mass spectrometry analysis identified the oxysterol as 5-cholesten-3β, 25-diol, disulfate (25HCDS), and confirmed the structure by comparing with a chemically synthesized compound. Administration of 25HCDS to human THP-1-derived macrophages or HepG2 cells significantly inhibited cholesterol synthesis and markedly decreased lipid levels in vivo in NAFLD mouse models. RT-PCR showed that 25HCDS significantly decreased SREBP-1/2 activities by suppressing expression of their responding genes, including ACC, FAS, and HMG-CoA reductase. Analysis of lipid profiles in the liver tissues showed that administration of 25HCDS significantly decreased cholesterol, free fatty acids, and triglycerides by 30, 25, and 20%, respectively. The results suggest that 25HCDS inhibits lipid biosynthesis via blocking SREBP signaling. We conclude that 25HCDS is a potent regulator of lipid metabolism and propose its biosynthetic pathway.
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影响因子：
3.9
作者：
Horton, JD
通讯作者：
Horton, JD
影响因子：
4.8
作者：
Cha, Ji-Young;Repa, Joyce J.
通讯作者：
Repa, Joyce J.
DOI：
10.1073/pnas.0404297101
发表时间：
2004-08-03
影响因子：
11.1
作者：
Chen, GX;Liang, GS;Brown, MS
通讯作者：
Brown, MS
类固醇生成急性调节蛋白的过度表达会增加微血管内皮细胞中 ATP 结合盒转运蛋白的表达 (bEnd.3)
影响因子：
5.1
作者：
Ning, Yan-xia;Ren, Shun-lin;Yin, Lian-hua
通讯作者：
Yin, Lian-hua
影响因子：
6.7
作者：
Ma, Y.;Ren, S.;Yin, L.
通讯作者：
Yin, L.