Stimulation of poly(ADP-ribose) synthesis by free radicals in C3H10T1/2 cells: relationship with NAD metabolism and DNA breakage

Abstract

We have studied the effect of H2O2 and O2- produced by xanthine and xanthine oxidase on NAD catabolism, poly(ADP-ribose) synthesis, and production of DNA single-strand breaks in C3H10T1/2 cells. The results show a correlation between the induction of DNA single-strand breaks, the decrease of NAD pool, and the accumulation of polymer. New techniques, based on affinity chromatography and reversed-phase high pressure liquid chromatography, have allowed an accurate determination of polymer contents and showed a 20-fold stimulation of polymer biosynthesis induced by active oxygen species. Inhibition experiments performed with 3-aminobenzamide have shown that the decrease in NAD levels after exposure of cells to active oxygen species was caused by stimulation of poly(ADP-ribosyl)ation and of another cellular process.

Proteasome inhibition results in increased poly-ADP-ribosylation: Implications for neuron death

“…Inhibition of PAR formation ameliorates neuron death in conditions associated with oxidative stress in vivo (Schraufstatter et al, 1985;Althaus and Richter, 1987;DeMurcia et al, 1988DeMurcia et al, , 1997Lautier et al, 1989;Szabo et al, 1996). The present study suggests that the ability of PARP inhibitors to provide possible therapeutic benefits may depend on the severity of proteasome inhibition and the time lapse between proteasome inhibition and application of PARP inhibitors.…”

“…The increase in PAR following application of proteasome inhibitors in the present study is likely mediated by the generation of single-and double-strand DNA breaks. Both single-and double-DNA strand breaks cause the activation of PARP (Schraufstatter et al, 1985;Lautier et al, 1989;Szabo et al, 1996), whereas inhibition of the proteasome results in DNA fragmentation and chromatin condensation (Imajoh-Ohmi et al, 1995;Drexler, 1997;Lopes et al, 1997;Boutillier et al, 1999;Keller et al, 1999;McDade et al, 1999;Wagenknecht et al, 1999;You et al, 1999). No increase in PARP protein levels was detected within the first 6 hr of lactacystin treatment (data not shown), which suggests increased PAR levels were not due to elevated levels of PARP.…”

“…In addition to proteasome inhibition, oxidative stress can cause the activation of poly-adenosine diphophateribose polymerase (PARP; Schraufstatter et al, 1985;Lautier et al, 1989;Szabo et al, 1996), which catalyzes the cleavage of NAD ϩ (nicotinamide adenine dinucleotide (oxidized)) into ADP-ribose and nicotinamide, covalent attaching polymers of ADP-ribose to histones and other nuclear proteins (Althaus and Richter, 1987;De Murcia et al, 1988. The consumption of large amounts of NAD ϩ during excessive or prolonged PARP activation can compromise cellular viability by contributing to a depletion of overall energy stores.…”

Poly(ADP‐Ribose) Polymerase in Bovine Retained and Not Retained Placenta

“…Poly(ADP‐ribosyl)ation is known to be involved in cellular response to different stimuli such as, among others, oxidant injury (Lautier et al. 1990; Cerutti et al.…”

DNA damage and repair in tumour and non-tumour tissues of mice induced by nicotinamide

“…PARP is activated by DNA strand breaks, which results in consumption of NAD (Jonsson et al, 1984b;Rawling et al, 1993) by producing longbranched polymers of the ADP-ribose moieties and free NAM (De Murcia et al, 1988). NAM, benzamide and 3-aminobenzamide (3aBAM) are all potent inhibitors of PARP at doses above 10-100uM (Rankin et al, 1989) by preventing production of polymer and reduction of the NAD pool after induction of DNA damage (Lautier et al, 1990(Lautier et al, , 1994Uchida et al, 1988). (Olsson et al, 1995).…”