Regulation Mechanism of DNA Synthesis in Rat Liver Regeneration

Abstract

A methodology of chemical kinetics was introduced to the investigation of the regulation network involved in DNA synthesis during rat liver regeneration following partial hepatectomy. Findings are as follows : 1. The rate-limiting enzymes in the DNA synthesis are thymidine kinase (TK) and the folate-dependent thymidylate synthase (TS), which catalyze the formation of thymidylate via the salvage and de novo pathways, respectively. 2. By evaluating the effect of drugs administration and the ablation of endocrine organs on activities of TS and TK which are S-phase specific enzymes, it was shown that the transition of the liver cells from G_1 state to S-phase takes place 10-12 h after partial hepatectomy, and was regulated by catecholamines released from the splanchnic nerves through hepatic α_1-receptors, and utilized calcium ion and metabolites of inositol turnover as intracellular messengers. 3. TS was purified from regenerating rat liver and characterized. Antiserum of TS was raised and used to establish the immunoblotting assay. The rise of TS activity during liver regeneration was due to the induction of TS and not to the activation by calcium ion.