Interaction of Eukaryotic DNA with Apolipoprotein A-I and Its Complexes with Glucocorticoids

摘要

A biochemically active complex of apolipoprotein A-I with tetrahydrocortisol was revealed and found to stimulate gene expression in hepatocytes. In native DNA isolated from rat liver, single-stranded regions appeared upon titration with a complex (apolipoprotein A-I)-tetrahydrocortisol, as demonstrated with a fluorescent probe. The small-angle X-ray scattering confirmed that the complex had an effect on the DNA secondary structure. With tetrahydrocortisol serving as a ligand, about 54 apolipoprotein A-I molecules were bound to a DNA molecule to break the hydrogen bonds between the heterocyclic base pairs. We suggest that a new biochemical mechanism underlies the cooperative effect of the high-density lipoproteins and cortisol in the regulation of gene expression in hepatocytes, which also involves resident liver macrophages. This mechanism implies DNA interaction with the (apolipoprotein A-I)-tetrahydrocortisol complex, appearance of single-stranded DNA regions in the binding sites, and subsequent initiation of gene transcription.