Biochemical characterization of ADP-ribose polymer metabolism in SLE.
The metabolism of poly(ADP-ribose) in peripheral blood mononuclear (PBM) cells was studied in 13 patients with systemic lupus erythematosus (SLE) and in 12 age and sex matched controls. Poly(ADP-ribose) polymerase activity was measured as the net accumulation of ADP-ribose polymers during the conversion of 32P-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-ribose/10 min/10(6) cells.  The mechanism of decreased ADP-ribose polymer accumulation was investigated. Measurements of turnover of the ADP-ribose polymers and its substrate, NAD+, showed that diminished ADP-ribose 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, kinetic studies of poly(ADP-ribose) polymerase activity and analyses of polymer size distribution suggested that the mechanisms of poly(ADP-ribose) synthesis in SLE cells is not altered but that the number of active poly(ADP-ribose) polymerase molecules is reduced.
Chen
H Y
HY
Department of Biochemistry, University of North Texas Health Science Center at Forth Worth, USA.
Pertusi
R M
RM
Kirkland
J B
JB
Rubin
B R
BR
Jacobson
E L
EL
D000328:Adult; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D011064:Poly Adenosine Diphosphate Ribose / Q000097:blood*; D011065:Poly(ADP-ribose) Polymerases / Q000097:blood
D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases