The Mechanism of Interacting Biologically Active Complexes Dehydroepiandrosterone- or Tetrahydrocortisol-Apolipoprotein A-I with DNA and their Role in Enhancement of Gene Expression and Protein Biosynthesis in Hepatocytes

Lev      Panin; Olga      Gimautdinova; Pavel      Kuznetsov; Fedor      Tuzikov

doi:10.2174/2212796811105010009

Abstract

Dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS) and tetrahydrocortisol (THC) with apolipoprotein A-I form the biologically active complexes able to interact specifically with eukaryotic DNA. This conjugate is highly cooperative and results in local splitting of DNA. Specific binding sites of steroid-apoA-I complexes are the (GCC/GGC)n sequences. At the sites of splitting, single-stranded regions sensitized to the action of S1-nuclease form. These regions are irregularly distributed over DNA. The formation of single-stranded DNA regions can promote the interaction with RNA-polymerase. Formation of the biologically active THC (DHEA)-apoA-I complexes is related with resident macrophages having 5α- and 5 β-reductase activity. These complexes greatly enhance the rate of protein biosynthesis in hepatocytes. The cortisol-apoA-I complex does not show such effect. So, the reduced forms of fascicular zone and reticular cortex adrenal zone hormones have synergism of action toward gene expression and protein biosynthesis. The intensification of tissues regeneration during the stress period as a result of given mechanism is discussed.

Keywords: Protein biosynthesis, DNA structure, tetrahydrocortisol, dehydroepiandrosterone, apolipoprotein AI, Biologically Active Complexes, Gene Expression, sulfate, hormones, adrenal cortex fascicular zone, luteinizing hormone, adrenal cortex, DNA, gluconeogenesis enzymes, hydroxyl group, eukaryotic, hepatocytes, High density lipoproteins, blood serum, ultracentrifugation, chylomicrones, ether-ethanol mixture, electrophoresis, UV-spectrum, RNA-polymerase, bacteriophage, Endocrinology, gentamycin, steroid hormones, leucine solution, alcohol-ether, Radioactivity, buffer, optical density, hybridization of DNA, densitometry data, X-ray film, X-ray Scattering, hepatocyte culture, cortisol, reticular, fascicular zones, 3-keto group, macrophages, agarose gel. UV-photo, ribosomal RNA, hypersensitive, hybridization, autoradiographs, BandScan program, stoichiometry, macromolecular, glucocorticoids