Increase of urinary extracellular-superoxide dismutase level correlated with cyclic adenosine monophosphate

Extracellular superoxide dismutase (EC-SOD) is a secretory protein that is the major SOD isozyme in extracellular fluids. Plasma EC-SOD levels are distributed in two discrete groups with the rare group having an enzyme with glycine instead of arginine-213, which causes a 10-fold higher serum level. Within the common phenotype group, the urinary EC-SOD level was significantly correlated with the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), but not with serum EC-SOD. EC-SOD appears not to be leaked from the plasma by glomerular filtration, but rather to be secreted from the renal tubule or its surrounding tissues. The urinary EC-SOD level was also significantly correlated with the urinary cyclic adenosine monophosphate (cAMP) level. cAMP analogues and adenylate cyclase modulators significantly stimulated the expression of EC-SOD but not other SOD isozymes in cultured fibroblast cell lines. Moreover, injection of parathyroid hormone, in Ellsworth-Howard tests, increased urinary EC-SOD accompanied with the elevations of urinary cAMP and NAG. Together these observations suggest that factor(s) that stimulate the adenylate cyclase-cAMP system regulate the urinary EC-SOD level.