Lysosome distribution and cathepsin B and L activity along the rabbit proximal tubule

The lysosomal-vacuolar system in the proximal tubule is responsible for reabsorption and degradation of proteins from the glomerular filtrate. In this study we mapped the activity of the lysosomal proteinases, cathepsins B and L, along the rabbit proximal tubule and compared cathepsin activities with the volume of lysosomes and endocytic vacuoles in the three segments of the proximal tubule. Individual tubules were dissected and assayed fluorometrically using two synthetic substrates, one specific for cathepsin B and a second for cathepsins B and L. The distribution of cathepsin activity along the proximal tubule was the same with each substrate, but there was a two- to threefold difference in the level of activity when expressed per millimeter of tubule. Enzyme activities were high in the initial 4-5 mm corresponding to the S1 segment and decreased in the pars recta to approximately 20% of the S1 value. Morphometric analysis revealed that the volumes of lysosomes and endocytic vacuoles per millimeter of tubule were significantly greater in the S1 segment than in the S2 and S3 segments. These findings suggest that the main site of protein degradation in the rabbit kidney under normal conditions is the initial 4-5 mm of the proximal tubule which corresponds to the S1 segment and is known to be a major site of protein reabsorption.