Effect of glucocorticoids and their complexes with apolipoprotein A‐I on the secondary structure of eukaryotic DNA

Abstract

ABSTRACT:The tetrahydrocortisol-apolipoprotein A-I complex specifically interacts with eukaryotic DNA isolated from rat liver. This interaction is highly cooperative and of a saturating nature. One DNA molecule binds about 54 molecules of the complex. Smallangle X-ray scattering has shown that hydrogen bonds between nitrous bases are destroyed and that single-stranded structures are formed at the interaction of the tetrahydrocortisolapolipoprotein A-I complex with eukaryotic DNA. The most probable site of binding the tetrahydrocortisol-apolipoprotein A-I complex with DNA is the sequence of the CC(GCC) n type entering the structure of many genes, among them the structure of the human apolipoprotein A-I gene. Oligonucleotide of this type has been synthesized. The association constant (K ass ) of its complexation was shown to be 1.66 ⅐ 10 6 M Ϫ1. Substitution of tetrahydrocortisol for cortisol in the complex results in a considerable decrease of K ass . IRspectroscopy study has shown that the interaction of tetrahydrocortisol with oligonucleotide CC(GCC) 3-5 is accompanied by the formation of hydrogen bonds via the CO-NH, PO 2 , and OH groups of desoxycytidinephosphate. The tetrahydrocortisol-apolipoprotein A-I complex alters the DNA secondary structure formed at the interaction with the hormone, causing the structural transition "order 3 tangle." It is assumed that in the GC-pairs of the given DNA sequence, tetrahydrocortisol initiates the rupture of hydrogen bonds, while the hydrophobic interactions between nitrous bases and apoA-I intensify this process.

Interaction of apolipoproteins A-I and E in the regulation of DNA, RNA, and protein biosynthesis in cultured rat hepatocytes

“…The hydroxyl group in position 3 directly participates in breaking of hydrogen bonds in sites of complex binding with DNA, i.e. hydrogen bonds in GC pairs break and close on the hydroxyl group of the hormone [12].…”

The Initiation Mechanisms of Gene Expression in Ascitic Hepatoma Cells Under the Action of Dehydroepiandrosterone in a Complex with Apolipoprotein A-I

“…These changes are caused by the formation of a hydrogen bond between one of H atoms of hormone and OH-group of desoxyribose as well as by a conformational change of desoxyribose (boats and chairs). A fraction of the chair conformation increases in the experiments, as this conformation is energetically more advantageous [19].…”

“…Besides, its peak and integral intensity increased 1.6 times. These are the asymmetric vibrations of P=O-bond [16,18] that indicate the formation of a hydrogen bond between CO-group of DHEAS (17-carbon atom) and P-OH-group of the duplex desoxyribose phosphate [19]. P=O and P-OH bonds are -conjugated, so their participation in the formation of hydrogen bonds with hormones changes their frequencies and intensities.…”

Effect of Apolipoprotein A-I Complex with Tetrahydrocortisone on Protein Biosynthesis and Glucose Absorption by Rat Hepatocytes

“…These complexes are formed in resident macrophages during cooperative capture of HDL and steroid hormones [14]. The molecular mechanisms underlying the effects of apoA-I-tetrahydrocompound complexes were studied [13]. Acceleration of biosynthetic processes is associated with stimulation of energy metabolism.…”