BIOCHEMICAL-CHARACTERIZATION OF ADP-RIBOSE POLYMER METABOLISM IN SLE

The metabolism of poly(ADP-ribose) in peripheral blood mononuclear (PB M) cells was studied in 13 patients with systemic lupus erythematosus (SLE) and in 12 age and sex matched controls. Poly(ADP-ribose) polymer ase activity was measured as the net accumulation of ADP-ribose polyme rs during the conversion of P-32-NAD to poly(ADP-ribose) in PBM cells in vitro. The control population showed a mean activity of 418 +/- 91( s.d.) pmol ADP-ribose/10 min/10(6) cells. The SLE population was more heterogeneous and showed a lower mean of 225 +/- 147(s.d.) pmol ADP-ri bose/10 min/10(6) cells. The mechanism of decreased ADP-ribose polymer accumulation was investigated. Measurements of turnover of the ADP-ri bose polymers and its substrate, NAD(+), showed that diminished ADP-ri bose polymer accumulation in SLE subjects resulted from decreased poly (ADP-ribose) synthesis and not from altered rates of polymer turnover or NAD utilization. Western blot analyses of enzyme protein levels, ki netic studies of poly(ADP-ribose) polymerase activity and analyses of polymer size distribution suggested that the mechanism of poly(ADP-rib ose) synthesis in SLE cells is not altered but that the number of acti ve poly(ADP-ribose) polymerase molecules is reduced.