No abstract

A complex of apolipoprotein A-I with steroid hormones containing reduced Δ4, 3-ketogroup in the A ring was shown to increase the rate of protein synthesis in the cultured rat hepatocytes. The biological activity of the hormones depends on the position of the oxygroup of the third carbonic atom and hydrogen at the fifth position of a carbonic atom. The cis-position is more preferable for the biological effect. The oxygroup at the third position of the A-ring may be replaced by the sulfo-group. The complex of dehydroepiandrosterone sulphate with apolipoprotein A-I increases the rate of protein biosynthesis in the cultured rat hepatocytes, which confirms the involvement of this hormone in the regulation of gene expression.

Production of recombinant human apolipoprotein A-I (apoA-I) in E. coli cells is described and its biological properties are compared with those of natural protein. Recombinant apoA-I was isolated as a chimeric polypeptide and then processed to a mature form apoA-I (rapo-I). We studied the ability of the resulting protein to penetrate into hepatocyte nuclei and regulate the rate of DNA biosynthesis in complex with estriol. Penetration of rapoA-I conjugated with FITC into hepatocyte nuclei was demonstrated. rapoA-I-estriol and apoA-I-estriol complexes induced similar increase in DNA biosynthesis rate in isolated hepatocytes, which confi rms functional similarity of the obtained recombinant mature protein (rapoA-I) and native human apoA-I.

Experiments on hepatocyte culture showed that apolipoprotein A-I-tetrahydrocortisol complex increases the rate of DNA, RNA, and protein biosynthesis measured by radioactive label incorporation. Apolipoprotein E acted as competitor of the apolipoprotein A-I-tetrahydrocortisol complex and abolished biological activity of the latter. We hypothesize that this mechanism of regulation plays an important role in processes of intracellular regeneration and proliferation.

Complexes of apolipoprotein A-I with tetrahydrocortisol and pregnenolone exhibit high biological activity and increase the rate of protein biosynthesis in the culture of rat hepatocytes. An important role in this process is played by reduced delta44-3-keto group in the A-ring of steroid hormones. A complex of apolipoprotein A-I and pregnenolone modulated the rate of protein biosynthesis in liver cells. Hence, the observed changes are not organ-specific for this steroid. Our results suggest that this mechanism of regulation play an important role in intracellular regeneration and proliferation.