Panin L E, Tuzikov F V, Tuzikova N A, Gimautdinova O I, Poliakov L M
Institute of Biochemistry, Siberian Division, Russian Academy of Medical Sciences, Novosibirsk, Russia.
Biofizika. 2000 Jul-Aug;45(4):611-9.
A biochemically active complex of apolipoprotein A-I with tetrahydrocortisol was revealed, which increases gene expression in hepatocytes. It was shown by the method of fluorescent probe that titration of rat liver DNA by the apolipoprotein A-I-tetrahydrocortisol complex leads to the appearance of single-stranded fragments. The effect of the complex on the secondary structure of native DNA was confirmed by the method of small-angle X-ray scattering. It was shown that approximately 54 apolipoprotein A-I molecules carrying tetrahydrocortisol as a ligand bind to one molecule of isolated native DNA, inducing a break of hydrogen bonds between the pair of nitrous bases. It is concluded that the cooperative effect of high-density lipoproteins and cortisol in the regulation of gene expression in hepatocytes with the participation of resident liver macrophages is accomplished by a new biochemical mechanism. This mechanism makes itself evident as a result of the interaction of DNA with the apolipoprotein A-I-tetrahydrocortisol complex, the appearance of single-stranded DNA regions in binding sites, and subsequent initiation of gene transcription.
发现了载脂蛋白A-I与四氢皮质醇的具有生化活性的复合物，该复合物可增加肝细胞中的基因表达。通过荧光探针法表明，用载脂蛋白A-I-四氢皮质醇复合物滴定大鼠肝脏DNA会导致单链片段的出现。通过小角X射线散射法证实了该复合物对天然DNA二级结构的影响。结果表明，约54个携带四氢皮质醇作为配体的载脂蛋白A-I分子与一个分离的天然DNA分子结合，诱导亚硝碱基对之间的氢键断裂。得出结论，高密度脂蛋白和皮质醇在驻留肝巨噬细胞参与下对肝细胞基因表达调控的协同作用是通过一种新的生化机制实现的。这种机制由于DNA与载脂蛋白A-I-四氢皮质醇复合物的相互作用、结合位点中单链DNA区域的出现以及随后基因转录的启动而显现出来。
