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 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.
Cesarone
C F
CF
Department of Physiological, Biochemical, and Cellular Sciences, Faculty of Science, University of Sassari, 07100 Sassari, Italy. cesarone@ssmain.uniss.it
Scarabelli
L
L
Demori
I
I
Balocco
S
S
Fugassa
E
E
D000818:Animals; D004261:DNA Replication; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D007037:Hypothyroidism / Q000150:complications / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000502:physiology*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D014284:Triiodothyronine; D011065:Poly(ADP-ribose) Polymerases; D004264:DNA Topoisomerases, Type I; D013974:Thyroxine