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1.
A common Ile796Val polymorphism of the human SREBP cleavage-activating protein (SCAP) gene 总被引:3,自引:0,他引:3
We identified a new common amino acid polymorphism of isoleucine/valine at codon 796 in exon 16 of the gene for human sterol
regulatory element binding protein (SREBP) cleavage-activating protein (SCAP), a central regulator of lipid synthesis and
metabolism in animal cells. It can be detected as an MslI restriction fragment length polymorphism. The allelic frequencies were: isoleucine (A) allele, 0.57 and valine (G) allele,
0.43. This polymorphism may be useful for genetic studies of disorders affecting intracellular lipid metabolism and hyperlipidemia.
Received: August 17, 1999 / Accepted: August 19, 1999 相似文献
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[目的]研究中药荷叶有效成分对非酒精性脂肪肝(NAFLD)模型小鼠的治疗作用及相关机制。[方法]通过蛋氨酸和胱氨酸联合缺乏饲料建立NAFLD模型小鼠,同时灌胃不同剂量荷叶碱,通过考察造模给药后各组小鼠体质量及血清生化指标,同时对肝组织分别进行苏木精-伊红(HE)染色和油红O染色,研究荷叶碱对NAFLD模型小鼠的治疗作用。此外提取造模给药后各组小鼠肝组织总核糖核酸(RNA),荧光定量核酸扩增检测(qPCR)法检测各组小鼠肝组织中胆固醇调节元件结合蛋白(SREBP)通路相关基因表达,初步探究荷叶碱缓解NAFLD的作用机制。[结果]荷叶碱能显著降低NAFLD模型小鼠体质量、血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆固醇(TC)及三酰甘油(TG)水平,同时荷叶碱可缓解NAFLD模型小鼠肝组织中脂肪变性,减少肝组织中脂质含量;此外,荷叶碱可下调NAFLD模型小鼠肝组织中SREBP通路相关基因SREBP-1、乙酰CoA羧化酶(ACC)、ATP-柠檬酸裂解酶(ACLY)及脂肪酸合酶(FASN)表达。[结论]荷叶碱对NAFLD具有明显的疗效,其作用机制可能与抑制肝细胞SREBP通路激活相关。 相似文献
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Satsuki Miyata Masashi Urabe Akira Gomi Mutsumi Nagai Takashi Yamaguchi Tomonori Tsukahara Hiroaki Mizukami Akihiro Kume Keiya Ozawa Eiju Watanabe 《Neurologia medico-chirurgica》2013,53(10):645-654
Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1R132H-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1R132H-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progressionof the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation. 相似文献
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目的 构建固醇调节元件结合蛋白裂解激活蛋白(SRREBP cleavage activating protein,SCAP)基因干扰(small interfering RNA,siRNA)和过表达重组腺病毒,观察其对ATDC5软骨干细胞增殖及凋亡的影响.方法 应用pAdEasyTM腺病毒载体系统构建重组腺病毒质粒pAd-SCAPsiRNA和pAdSCAP,在HEK293细胞中分别包装和扩增.RT-PCR和Western blot检测ATDC5细胞中SCAP的表达,流式细胞仪检测SCAP腺病毒对ATDC5细胞周期和凋亡的影响,Western blot检测凋亡相关蛋白Cleaved Caspase-3、p-JNK的表达.结果 成功获腺病毒siSCAP(滴度为2.5 × 1010PFU/mL)和Ad-SCAP(滴度为3.0×10n PFU/mL).RT-PCR和Western blot结果表明:siSCAP和Ad-SCAP能分别有效抑制和增强ATDC5细胞中SCAP的表达.流式细胞仪检测结果表明:与正常组和空病毒组比较,siSCAP腺病毒处理组S期细胞比例升高15.45%和16.07% (P <0.05),Ad-SCAP组比例降低14.27%和13.45%(P<0.05);siSCAP组细胞凋亡率降低13.10%和11.50% (P <0.05),Ad-SCAP组升高10.51%和10.17% (P <0.05).Western blot检测结果与流式细胞仪检测结果一致.结论 成功构建SCAP腺病毒;敲低SCAP能促进ATDC5细胞增殖并抑制凋亡;过表达SCAP则抑制增殖、促进凋亡. 相似文献
6.
Li T.Zhao L.-P.Yu C.-C.Tian N.Fan C.-L. 《中国药理学通报》2018,(7):1020-1024
Aim To investigate the effect of squalene on LDLR expression in HepG2 cells and its mechanism of down-regulated cholesterol. Methods The proliferation of HepG2 cells exposed to squalene at different concentrations was measured by MTT assay. The effect of squalene on the expression of LDLR in HepG2 cells was measured by flow cytometry and fluorescence mi-croscopy. The effect of different concentrations of squalene on the interaction between SCAP and Insig2, two key protein molecules of SREBP pathway, was assayed by FRET technology. Results MTT results showed that squalene had inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner. Flow cytometry and fluorescence microscopy results showed that squalene enhanced LDLR expression in HepG2 cells compared with the control group. The results of FRET technology revealed that compared with model control group, the YFP fluorescence value in Squalene group dramatically declined, and the YFP fluorescence value of each drug group decreased with the range of 5-25 |xmol L1 squalene concentration. Conclusions Squalene may promote the expression of LDLR in HepG2 cells through inhibiting the interaction between SCAP and Insig2 proteins in SREBP pathway, which may confirm that squalene is a potential novel drug for the down-regulation of cholesterol level. © 2018 Publication Centre of Anhui Medical University. All rights reserved. 相似文献
7.
Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ~ 6500 unique proteins quantified, ~ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. 相似文献
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Huiling Luan Zhaojiong Huo Zifeng Zhao Shoukang Zhang Yihai Huang Yanhui Shen Pu Wang Junxiao Xi Jingyu Liang Feihua Wu 《Phytotherapy research : PTR》2020,34(6):1455-1466
High levels of consumption of saturated lipids have been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance (IR). Scutellarin (Scu) is one of the effective traditional Chinese medicines considered beneficial for liver diseases and diabetes. In this study, we investigated the effect of Scu on IR and lipid metabolism disorders in vitro and in high fat diet (HFD)‐fed mice. In vitro, we found that Scu decreased insulin‐dependent lipid accumulation and the mRNA expression of CD36, Fasn, and ACC in PA‐treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation and improved the insulin signalling pathway. Moreover, Scu downregulated mammalian target of rapamycin (mTOR) phosphorylation and the n‐SREBP‐1c protein level and also reduced lipid accumulation via the mTOR‐dependent pathway, as confirmed by the molecular docking of Scu to mTOR. In HFD‐fed C57BL/6 mice, Scu improved oral glucose tolerance, pyruvate tolerance and the IR index and also increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR phosphorylation, and decreased the SREBP‐1c level in the liver. Taken together, these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte lipid metabolism via the mTOR‐dependent pathway through SREBP‐1c suppression. 相似文献