Influence of starvation on the activities and localization of cathepsin D and other lysosomal enzymes in hearts of rabbits and mice

An investigation was made in mice and rabbits of the effects of starvation on the activities and cellular localization of lysosomal enzymes in cardiac muscle of the left ventricle. The specific activity of cathepsin D was increased in the atrophying hearts of mice, by 14% after one day and by 26% after 3 days. Simultaneously, the proportion of the enzyme activity that was nonsedimentable during centrifugation at 40 000 g rose significantly, suggesting increased fragility of lysosomes or release of enzyme from lysosomes into the cytosol. In the same hearts protein concentration and the activities of acid phosphatase and beta-acetylglucosaminidase remained unchanged. Changes were similar in rabbit hearts except that specific cathepsin D activity was increased more (46%) and changes in the proportion of the activity that was nonsedimentable were less marked. Immunofluorescent staining for rabbit cathepsin D revealed that this acid proteinase was localized in lysosome-like particles in both interstitial cells and muscle fibres in hearts of normal animals. After 3 days starvation there was no detectable change in interstitial cells, but in the muscle fibres particulate staining was greater and, in addition, intense diffuse cytoplasmic staining was observed. The results indicate that cardiac muscle, like liver but unlike skeletal muscle, develops a significant increase in the activity of the lysosomal protease cathepsin D during starvation. The change occurs specifically in myocytes rather than in interstitial cells. The results suggest a possible role for cathepsin D in contributing to the development of cardiac atrophy and net protein catabolism during prolonged starvation.