Inhibition of cellular autophagy in kidney tubular cells stimulated to grow by unilateral nephrectomy.

Cytoplasmic growth (hypertrophy) presupposes a positive metabolic balance brought about by increased anabolic and/or decreased catabolic processes. Degradation of cytoplasmic components takes place in autophagic vacuoles (AVs) whose volume fraction may be taken as a measure of the relative rate of degradation of cytoplasmic components. Male adult Sprague-Dawley rats (n = 80) were unilaterally nephrectomized (n = 40) or sham-operated (n = 40) and were killed 3.5-57.5 h p.o. The volume density of AVs in parenchymal cells of renal cortical convoluted tubules was determined morphometrically by systematic evaluation of large test fields in the electron microscope. During compensatory renal growth, the volume densities of autophagic vacuoles were reduced at day 0 (3.5-8 h p.o.), day 1 (20.5-33.5 h p.o.) and day 2 (44.5-57.5 h p.o.) by 49% (p less than 0.01), 43% (p less than 0.05), and 19% (n.s.), respectively, when compared with sham-operated controls. No decrease, and even an increase, in the AV-volume fraction was found in liver parenchymal cells of the unilaterally nephrectomized animals. This indicates that inhibition of autophagy is not a general response after unilateral nephrectomy, but is confined to the growing kidney, where it may represent a significant factor in the increase of cytoplasmic mass.