Changes in lysosomal cathepsins during liver regeneration.

The effect of 2/3 hepatectomy in the adult rat on the specific and total activities of two lysosomal endopeptidases, cathepsins B1 and D, has been examined. The specific activity of both enzymes fell rapidly following hepatectomy when compared to paired, sham-operated controls. When changes in total protein were compared to changes in cathepsins B1 and D, all three decreased in a parallel fashion for the first 18 h. At 24 h, total liver protein increased rapidly while cathepsins B1 and D continued to decrease. Cathepsin B1 fell to a level of 12% of non-operated control levels at 36 h, while total protein was already back to 40% of control levels. In contrast to the decreases in the activities of the cathepsins, there was an increase in the activities of lactate dehydrogenase and malate dehydrogenase during the first two days of regeneration. The clear lag in replacement of the cathepsins relative to other liver proteins following partial hepatectomy suggests that cathepsin activity is selectively controlled and that lowering the levels of cathepsins B1 and D may play an important role in the decreased degradation of protein seen during the early phases of liver regeneration.