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

Lev   Evgenievich   Panin; Valery   Georgievich   Kunitsyn

Abstract

Experiments with a cell culture of ascitic hepatoma A/He showed that dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) in a complex with apolipoprotein A-I (apoA-I) stimulate synthesis of DNA and protein, whereas the hormones themselves do not have such an effect. The initiation mechanism of these processes was studied with synthetic oligonucleotides of (GCC)n type. A search over the international database (Gene Bank) revealed the presence of repetitions of this type in various mammalian genes, in particular, in the structure of promoter regions. IR spectroscopy was used to study the interaction mechanism of DHEA and DHEAS as well as their apoA-I complexes with the duplex CC(GCC)5 . GG(CGG)5. It was found that DHEA and DHEAS increase the orderliness of CC(GCC)5 . GGG(CGG)5 duplex according to the order – order structural transition, whereas their complexes DHEAS – apoA-I and DHEA – apoA-I incubated with the duplex, on the contrary, initiate disordering of the duplex secondary structure (the order – disorder transition), thus leading to its melting. Interaction of the duplex with these hormones results in the formation of hydrogen bonds involving SO3H, CO-groups and CH-bonds of DHEAS, and OH-group of the A-ring, CO and CH-bonds of DHEA. Active site of the duplex comprises CO, NH-bonds of nitrous bases, PO2 – and O4-C4-C5-O5- bonds of the sugar-phosphate chain. The role of duplex melting under the action of DHEA – apoA-I and DHEAS – apoAI complexes in the initiation mechanism of gene expression as well as the enhancement of DNA and protein synthesis are discussed.

Keywords: Hepatocarcinoma, DNA and protein synthesis, secondary structure of oligonucleotides, dehydroepiandrosterone, dehydroepiandrosterone sulfate, apolipoprotein A-I, IR spectroscopy

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