Inhibitors of poly (ADP-ribose) polymerase suppress lipopolysaccharide-induced nitrite formation in macrophages.
Stimulating bone marrow derived macrophages with LPS results in the induction of NO-synthase as measured by NO2- formation. Inhibitors of poly(ADP-ribose)polymerase, namely nicotinamide, 3-aminobenzamide and 3-methoxybenzamide, prevented NO2- formation in a dose dependent manner. Inhibition was most effective if the inhibitors were added at the same time as LPS. When added 10 h after exposure to LPS, a time at which expression of the enzyme had reached its maximum, no inhibition was observed. The inhibitors also blocked early events in activation such as protein and RNA-synthesis as well as DNA-synthesis. Thus prevention of NO2- formation may be related to inhibition of these events. Activation of macrophages by LPS was not accompanied by an increase but rather by a small decrease in ADP-ribosyltransferase activity. Whether this decrease plays a physiological role in activation needs further exploration.
Hauschildt
S
S
Institute of Immunobiology, University of Freiburg, FRG.
Scheipers
P
P
Bessler
W G
WG
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001854:Bone Marrow Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D001549:Benzamides; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; C025160:3-aminobenzamide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C025159:3-methoxybenzamide