Poly(ADP-ribose) polymerase is affected early by thyroid state during liver regeneration in rats

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 synthe...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2000-12, Vol.279 (6), p.G1219-G1225
Main Authors: Cesarone, C F, Scarabelli, L, Demori, I, Balocco, S, Fugassa, E
Format: Article
Language:English
Subjects:
Animals
DNA Replication
DNA Topoisomerases, Type I - metabolism
Hypothyroidism - complications
Hypothyroidism - physiopathology
Liver Regeneration - physiology
Male
Phosphorylation
Poly(ADP-ribose) Polymerases - metabolism
Rats
Rats, Wistar
Thyroid Gland - physiology
Thyroxine - blood
Triiodothyronine - blood
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Summary: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 [(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.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.2000.279.6.G1219