Search

Cesarone, C. F., L. Scarabelli, I. Demori, S. Balocco, and E. Fugassa. Poly(ADP-ribose) polymerase is affected early by thyroid state during liver regeneration in rats. Am J Physiol Gastrointest Liver Physiol 279: G1219-G1225, 2000.--Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme involved in DNA synthesis, DNA repair, and cell replication and transformation, also plays a role in the early steps of liver regeneration induced by partial hepatectomy (PH). PARP and DNA topoisomerase I (Topo I) activities and de novo DNA synthesis were studied during liver regeneration in rats with altered thyroid state. Hepatic PARP activity, evaluated as [sup.32]P]NAD incorporated into isolated liver nuclei, was inhibited in hyperthyroid rats and increased in hypothyroid animals. In both euthyroid and hyperthyroid rats PARP activity was rapidly stimulated, peaking 6 h after PH. In hypothyroid animals, an early decrease in activity was found, at a minimum of 6 h after PH, followed by an early onset of DNA synthesis. An inverse relationship between PARP and Topo I activities was a shared feature among euthyroid, hypothyroid, and hyperthyroid rats. Together these data show that, in replicating hepatocytes, thyroid hormones exert a regulatory role on PARP activity, which reflects the control of a number of nuclear proteins involved in DNA metabolism. poly(ADP-ribosyl)ation; DNA synthesis; DNA topoisomerase I; partial hepatectomy; liver growth

The insulin-like growth factor (IGF) binding proteins (IGFBPs) are important regulators of cell growth produced by different tissues. The IGFBPs regulate cell growth by modulating the activity and bioavailability of IGFs. The evidence that IGFBP-1 is a liver-specific immediate-early gene highly induced after 70% partial hepatectomy (PHx) suggests a role for the IGF-IGFBP system in hepatic regeneration. In this work we analyzed the effect of PHx on the expression of IGFBP-4, which is highly produced by the liver and very abundant in rat serum. Our results show a marked increase in hepatic IGFBP-4 mRNA levels 6-12 h after PHx and no significant change in sham-operated control animals. A parallel rise in IGFBP-4 transcript abundance was observed in the kidneys of PHx rats but not in sham-operated animals. Moreover, ligand blot analysis demonstrated that serum IGFBP-4 levels began to increase 12-24 h after surgery, consistent with the rise in the corresponding mRNA. This enhancement in IGFBP-4 production after PHx could be part of a fine regulatory mechanism to modulate IGF activity during liver regeneration.