Role of ADP-Ribosylation in Activated Monocytes/Macrophages
Stimulating monocytes/macrophages with bacterial lipopolysaccharide (LPS) results in TNF-α, IL-1, IL-6 and nitrite (NO2 -) formation. Inhibitors of poly(ADP-ribose)polymerase inhibit release of these mediators by preventing mRNA expression indicating that ADP-ribosylation plays a crucial role in the synthesis of these mediators. Furthermore we present evidence that ADP-ribosylation is involved in modifying cellular proteins. In murine macrophages a 33 kDa cytosolic protein could be identified that in response to LPS changed its state of ADP-ribosylation, and in human monocytes we showed that the inhibitor nicotinamide prevents LPS induced phosphorylation of two cytosolic proteins of 36 kDa and 38 kDa (p36/38) LPS. Taken together these data indicate that protein modification by ADP-ribosylation may control cellular processes involved in distinct steps of monocyte/macrophage activation.
KeywordsNitrite Adenine Dinucleotide Phospho Nicotinamide
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- 1.Hayaishi, O. & K. Ueda eds. 1982. ADP-Ribosylation Reactions: Biology and Medicine. Academic Press, New York.Google Scholar
- 3.Molina Y Vedia, L.B. McDonald, B. Reep, B. Brüne, M. Di Silvio, T.R. Billiar & E.G. Lapetina. 1992. Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehy-drogenase inhibits enzymatic activity and increases endogeneous ADP-ribosylation. J. Biol. Chem. 267: 24929–24932.Google Scholar
- 8.Pellat-Deceunynek, C, J. Wietzerbin & J.C. Drapier. 1994. Nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages. Biochem. J. 297: 53–58.Google Scholar