Abstract：
UNASSIGNED: Sirtuin1 (SIRT1) plays a crucial role in the pathophysiology of non-alcoholic fatty liver disease. We investigated the mechanistic role of galbanic acid (Gal) as a regulator of SIRT1 in silico and in vitro.
UNASSIGNED: HepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns.
UNASSIGNED: The semi-quantitative results of Oil red (p < .03) and TG level (p < .009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p < .05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar.
UNASSIGNED: Computational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells.
UNASSIGNED: HepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns.
UNASSIGNED: The semi-quantitative results of Oil red (p < .03) and TG level (p < .009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p < .05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar.
UNASSIGNED: Computational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells.
摘要：
■Sirtuin1（SIRT1）在非酒精性脂肪性肝病的病理生理学中起着至关重要的作用。我们研究了galbanicacid（Gal）在计算机和体外作为SIRT1调节剂的机制作用。
■在存在或不存在SIRT1特异性抑制剂EX-527的情况下，用Gal处理HepG2细胞，24小时。通过RT-PCR和Western印迹测量Sirtuin1基因和蛋白质表达，分别。已将其与SIRT1的变构统治（PDBID：4ZZJ）对接，以研究Gal对SIRT1的影响，然后在100ns内研究了蛋白质和复杂分子动力学（MD）模拟。
■油红（p<.03）和TG水平（p<.009）的半定量结果显示，通过用Gal处理，脂质积累显着减少。此外，SIRT1的基因和蛋白表达显著增加(p<0.05)。MD研究表明，蛋白质结构的平均均方根偏差（RMSD）约为0.51和复合物的0.66。蛋白质和复合物的平均回转半径（Rg）为2.33和2.32µ，分别,均方根波动(RMSF)的模式几乎相似。
■计算研究表明，Gal可以作为SIRT1配体使用，因为它不会干扰蛋白质的结构，和其他实验研究表明，用SIRT1抑制剂Gal处理增加脂肪在HepG2细胞中的积累。
■在存在或不存在SIRT1特异性抑制剂EX-527的情况下，用Gal处理HepG2细胞，24小时。通过RT-PCR和Western印迹测量Sirtuin1基因和蛋白质表达，分别。已将其与SIRT1的变构统治（PDBID：4ZZJ）对接，以研究Gal对SIRT1的影响，然后在100ns内研究了蛋白质和复杂分子动力学（MD）模拟。
■油红（p<.03）和TG水平（p<.009）的半定量结果显示，通过用Gal处理，脂质积累显着减少。此外，SIRT1的基因和蛋白表达显著增加(p<0.05)。MD研究表明，蛋白质结构的平均均方根偏差（RMSD）约为0.51和复合物的0.66。蛋白质和复合物的平均回转半径（Rg）为2.33和2.32µ，分别,均方根波动(RMSF)的模式几乎相似。
■计算研究表明，Gal可以作为SIRT1配体使用，因为它不会干扰蛋白质的结构，和其他实验研究表明，用SIRT1抑制剂Gal处理增加脂肪在HepG2细胞中的积累。
