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Published on: July 14, 2023
Hepatic poly(ADP-ribose) polymerase activity in rat is controlled by thyroid hormones
C F Cesarone1, L Scarabelli, P Giannoni
1Institute of General Physiology, University of Genoa, Italy.
Biochemical and Biophysical Research Communications
|September 30, 1994
Summary
Thyroid hormones, specifically L-triiodothyronine, transiently inhibit poly(ADP-ribose) polymerase activity in rats. This effect, observed in vivo and in vitro, suggests nuclear receptors mediate thyroidal regulation of this enzyme.
Area of Science:
- Biochemistry
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormones regulate numerous physiological processes.
- Poly(ADP-ribose) polymerase (PARP) is a key enzyme involved in DNA repair and other cellular functions.
- The interplay between thyroidal state and PARP activity remains incompletely understood.
Purpose of the Study:
- To investigate the in vivo and in vitro effects of thyroidal state and L-triiodothyronine on poly(ADP-ribose) polymerase activity.
- To determine if thyroid hormone-induced changes in PARP activity involve alterations in catalytic protein levels.
- To explore the potential role of nuclear receptors in mediating thyroidal regulation of PARP.
Main Methods:
- Investigated PARP activity in eu- and hypothyroid rats treated with L-triiodothyronine.
- Assessed enzyme activity in isolated liver nuclei exposed to varying L-triiodothyronine concentrations in vitro.
- Utilized amiodarone as an antagonist to probe the involvement of nuclear receptors.
Main Results:
- Untreated hypothyroid rats exhibited increased basal PARP activity.
- L-triiodothyronine treatment in both eu- and hypothyroid rats caused a rapid, transient decrease in PARP activity, not linked to catalytic protein reduction.
- In vitro, L-triiodothyronine progressively inhibited PARP activity in a dose-dependent manner.
- Amiodarone pretreatment blocked the inhibitory effect of L-triiodothyronine, implicating nuclear receptors.
Conclusions:
- Thyroidal state significantly influences poly(ADP-ribose) polymerase activity.
- L-triiodothyronine acutely modulates PARP activity through a mechanism independent of catalytic protein levels.
- Nuclear receptors likely play a crucial role in mediating the thyroid hormone's effect on PARP activity.
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