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Poly(ADP-ribose) polymerase-1 is a novel nuclear target for cholinergic receptor signaling in the hippocampus
R P Strosznajder1, H Jesko, A Adamczyk
1Department of Respiratory Research, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. roberts@cmdik.pan.pl
Abstract:
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation. The aim of this study was to investigate the role of PARP-1 in muscarinic cholinergic receptor signaling. Our data indicate that activation of muscarinic cholinergic receptors by carbachol (1mM) in the presence of GTP gamma S evoked a significant enhancement of PARP activity in the adult rat hippocampus. Moreover, TMB-8 (10 microM), an antagonist of inositol 1, 4, 5 trisphosphate (IP(3)) receptor prevented the activation of PARP-1, which indicates that IP(3) /Ca(2+) signaling is involved in this pathway. The diacylglycerol (DAG)-regulated protein kinase C (PKC) inhibitor (GF109203X) (1 microM) only slightly enhanced PARP activity in hippocampal nuclear fractions, which suggests that DAG/ PKC is not involved in PARP activation.
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