Acid ribonuclease and alkaline ribonuclease isoenzymes in plasma of patients with decreased glomerular filtration rate

Removal of low molecular weight proteins from plasma by kidneys depends on glomerular filtration rate (GFR), protein-glomerular membrane electric charge, steric interactions and a number of functionally active nephrons present in the kidneys. There is a well documented relationship between the concentration of low molecular weight proteins in plasma and GFR value in patients with impaired renal function. Accumulation of low molecular weight proteins in plasma along with a decrease in GFR value may in the long run enhance formation of protein tissue deposits known as various forms of amyloidosis. In this paper we present studies on plasma concentrations of acid leukocyte-type ribonuclease (RNase) and alkaline pancreatic-type RNase and GFR value in 54 patients with renal failure. RNase isoenzymes' activities were assayed by measuring their enzyme activities manifested as ability to decompose yeast RNA and assay of digestion products' concentration by spectrophotometry. The studies show that decreasing filtration rate produces an increase in serum activities of both acid and alkaline RNases, which is proportional to the logarithm of GFR value. However, the increase rate vs. GFR value is by four times higher for acid RNase then for alkaline RNase. Acid RNase in human plasma is mostly of leukocytic origin and differs from pancreatic-type alkaline RNase, which is of pancreatic origin. The obtained results may suggest that leukocyte originating proteins essentially contribute to low molecular weight protein accumulation in plasma of patients with chronic renal insufficiency.

Effects of recombinant leukocyte interferon on ribonuclease activities in serum in chronic hepatitis B

Alkaline ribonuclease (RNase; EC 3.1.27.5) activities and 2',5'-oligoadenylate synthetase (2-5 AS; no EC no. assigned) activities in serum were measured in nine patients with hepatitis B e antigen-positive chronic hepatitis B before, during, and after treatment with recombinant human interferon alpha-2b for four weeks at daily doses ranging from 3 to 10 mega-units. Alkaline RNase activities in serum significantly increased from 65.8 +/- 9.5 units/L (mean +/- SD) to 84.3 +/- 11.9 units/L after the first week of therapy (P less than 0.001). (One unit of RNase activity is defined as that increasing the absorbance at 260 nm by 1.0 in 1 min). This increase persisted during and until two weeks after the end of the therapy, at which time the mean RNase activity in serum was still significantly increased (70.8 +/- 9.4 units/L, P less than 0.01). Before therapy, phosphocellulose chromatography of RNase showed five active peaks of enzyme activity, which were similar to that observed even when RNase activity increased immediately after therapy. There was a close correlation between RNase activities and the logarithm of 2-5 AS activities, measured simultaneously in each patient. We conclude that recombinant alpha-interferon therapy increases RNase activities in serum, associated with the increased 2-5 AS activities.