Poly(ADP-ribose) polymerase-1 inhibition protects the brain against systemic inflammation
Grzegorz A Czapski1, Magdalena Cakala, Barbara Gajkowska
1Department of Cellular Signalling, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., PL-02106 Warsaw, Poland. grzegorz@cmdik.pan.pl
Abstract:
Poly(ADP-ribose) polymerase-1 (PARP-1) is involved in DNA repair, but its overactivation can induce cell death. Our aim was to investigate the role of PARP-1 in activation of programmed cell death processes in the brain during systemic inflammation. Our data indicated that lipopolysaccharide (1mg/kgb.w., i.p.)-evoked systemic inflammation enhanced PARP-1 activity in the mouse brain, leading to the lowering of beta-NAD(+) concentration, to translocation of apoptosis inducing factor from mitochondria to the nucleus, and to enhanced lipid peroxidation. Inhibitor of PARP-1, 3-aminobenzamide (30 mg/kgb.w., i.p.), protected the brain against prooxidative and cell death processes, suggesting involvement of PARP-1 in systemic inflammation-related processes in the brain.
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