FORMATION OF RENAL MEDULLARY LYSOSOMES DURING POTASSIUM-DEPLETION NEPHROPATHY

Abstract

The biochemical correlates of droplet formation in renal inner medullary cells of K-deficient rats were studied. An increase in the activities of 5 hydrolytic enzymes typical of lysosomes was associated with an increase in the number and size of droplets observed during progressive K depletion. Acid phosphatase activity increased 7-fold whereas .beta.-glucuronidase, .beta.-galactosidase, cathepsin and acid DNase increased 2- to 4-fold in medullary homogenates at 25 days of depletion. Following K repletion the activities returned to normal at a rate dependent upon the duration of K depletion. The decreases in enzyme activities were associated with a concomitant rapid disappearance of the droplets from medullary cells. Protein synthesis for new droplet enzyme formation was studied by measuring the rate of 14C-leucine incorporation into protein in medullary slices. The rate increased at 1 day of depletion and reached a maximum which was 139% higher than control after 7 days of depletion. In droplets isolated from medullary tissue during progressive K depletion the rate of protein labeling with 14C-leucine and acid phosphatase specific activity increased in parallel. When droplet proteins were separated by gel electrophoresis, acid phosphatase activity was detected in a protein band which had been labeled with 14C-leucine, thereby suggesting new enzyme protein formation. The increase in enzyme and protein synthesis and a previously demonstrated increase in phospholipid synthesis and membrane formation indicated that K depletion induced specific alterations in renal inner medullary cell metabolism which resulted in increased lysosome formation.