Regulation of protein turnover versus growth state

Abstract

Yoshida AH-130 ascites hepatoma cells were grown in rats and were examined by quantitative electron microscopy 4 days (exponential growth phase) and 10 days (stationary phase) after intraperitoneal inoculation. No significant differences between growing and growth-inhibited tumors were found in the composition of the cytoplasm, except for a slight increase in the volume fraction of mitochondria (from 9.6 to 12.1%) and, in particular, a prominent (4.2-fold) increase in the volume fraction of early stages of autophagic vacuoles (from 0.31 × 10-4 at day 4 to 1.37× 10-4 at day 10;P 0.001). At the same time, the rate of cell protein degradation was increased twofold, namely from 0.67%/h at day 4 to 1.37%/h at day 10, as measured in vitro after labeling cells with 3H-leucine in vivo. Such elevated proteolytic activity was entirely suppressed by ammonia, which inhibits the lysosomal pathway for protein degradation. The data show that: (i) the regulation of autophagic degradation of cytoplasmic constituents depending on the growth state was maintained in these tumor cells, and (ii) the increase in autophagy measured by morphometric analysis contributed to, yet did not quantitatively explain, the acceleration of protein degradation characterizing the transition from the logarithmic growth phase to the growth-inhibited state.