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Lupus
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Biochemical characterization of ADP-ribose polymer metabolism in SLE

H-Y. Chen

Department of Biochemistry & Molecular Biology, University of North Texas Health Science Center at Forth Worth

RM Pertusi

Department of Medicine, University of North Texas Health Science Center at Forth Worth

JB Kirkland

Department of Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada, N1G2W1

BR Rubin

Department of Medicine, University of North Texas Health Science Center at Forth Worth

EL Jacobson

Department of Biochemistry & Molecular Biology, University of North Texas Health Science Center at Forth Worth, Department of Medicine, University of North Texas Health Science Center at Forth Worth

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/106 cells. The SLE population was more heterogeneous and showed a lower mean of 225 ± 147(s.d.) pmol ADP-ribose/ 10 min/106 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 mechanism of poly(ADP-ribose) synthesis in SLE cells is not altered but that the number of active poly(ADP-ribose) polymerase molecules is reduced.

Key Words: poly(ADP-ribose) polymerase • poly(ADP-ribose) glycohydrolase • NAD+

Lupus, Vol. 5, No. 1, 14-21 (1996)
DOI: 10.1177/096120339600500105
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