Increase of Mono(ADP-Ribose) Protein Conjugate Levels in Rat Liver. Induced by Nicotinamide Administration

Abstract

Protein-bound mono(ADP-ribose) residues were quantitated in the livers of nicotinamide-treated and control rats. Nicotinamide administration led to a rise in NAD® (2.5-fold) and in protein-bound mono (ADP-ribose) residues (1.5-fold). This increase was higher in the NH 2 OH-sensitive mono(ADP-ribose) protein conjugates than in the NH 2 OH-resistant subfraction. NADH, NADP and NADPH levels did not change significantly under these conditions.The findings show that nicotinamide induced an increased ADP ribosylation of new acceptor sites, and not merely an elongation of pre-existing (ADP-ribose)fl chains. A correlation of the NAD® concentration and the extent of postsynthetic modification of nuclear proteins by mono(ADP-ribose) residues was not restricted to nicotinamide-induced changes. It was also seen in various tissues with widely differing NAD® levels.

Modification of proteins by mono(ADP-ribosylation) in vivo

“…It is encouraging, therefore, that our value of 5.50 nmol/mg of DNA (31.8 pmol/mg of protein) for arginine-linked ADP-ribose residues is reasonably close to their value of 7.12 nmol/mg of DNA for ADP-ribose bound via hydroxylamine-resistant linkages. The levels of arginine-linked ADP-ribose residues we detected were about 400-fold higher than ADP-ribose units in poly-(ADP-ribose) (14.3 pmol/mg of DNA) (Jacobson et al, 1983) but still represented less than 1% of the total NAD content in rat liver (Bredehorst et al, 1980). These quantitative relationships, as well as the results suggesting that at least two distinct types of ADP-ribose-protein linkages exist in vivo, are also in general agreement with the findings of Hilz et al (1982a,b).…”

Prevention of Nitric Oxide-Induced Neuronal Injury Through the Modulation of Independent Pathways of Programmed Cell Death

“…Proteolytic fragments of PARP, such as the 85 kDa form, were not evident suggesting subsequent PARP cleavage during NO administration similar to other ischemic injury paradigms (Taylor et al, 1997). In addition, because nicotinamide alone can lead to the ribosylation of PARP (Bredehorst et al, 1980), the absence of the 85 kDa form of PARP is not a result of possible ribosylation of epitope binding sites. It is conceivable that nicotinamide maintains DNA integrity through at least two possible pathways that involve PARP.…”