AJP - Renal Physiology, Vol 253, Issue 6 1290-F1301, Copyright © 1987 by American Physiological Society
Lysosome distribution and cathepsin B and L activity along the rabbit proximal tubule
K. M. Madsen and C. H. Park
Division of Nephrology, University of Florida College of Medicine, Gainesville 32610-0224.
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.
