Poly(ADP-ribose) polymerase-1 inhibition protects the brain against systemic inflammation.
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.
Czapski
Grzegorz A
GA
Department of Cellular Signalling, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., PL-02106 Warsaw, Poland. grzegorz@cmdik.pan.pl
Cakala
Magdalena
M
Gajkowska
Barbara
B
Strosznajder
Joanna B
JB
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D007249:Inflammation / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008854:Microscopy, Electron; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D001549:Benzamides; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1