Inhibited autophagic degradation of cytoplasm during compensatory growth of liver cells after partial hepatectomy

Abstract

The livers from 56 sham-operated and 56 partially hepatectomized male albino rats killed 4--81 h after operation were investigated by electron microscopic morphometry. Following partial hepatectomy, the principal changes in volume fractions in the hepatocellular cytoplasm were: decrease of glycogen and, to a lesser extent, of mitochondria together with considerable increase of fat droplets. The volume fraction of microbodies (= peroxisomes) showed no significant difference between control and regenerating liver. By evaluating large test fields of about 40,000 micrometers 2 sectioned cytoplasm per animal it could be demonstrated that the volume fraction and the numerical density of autophagic vacuoles (AV's) were significantly reduced after partial hepatectomy. The extent of this reduction depended on the postoperative time interval. AV's were reduced by 75% at day 0 (4--17 h p.o.), by 98% at day I (19--33 h p-o.), by 75% at day II (43--57 h p.o.), and still by 50% at day III (67--81 h p.o.). The different types of AV's, defined on the basis of the different cytoplasmic components enclosed, were reduced to similar extent during the respective time periods. The reduction of AV's seems to be specific for the regenerating organ since no significant differences in the volume fraction of AV's could be found in the proximal tubular cells of the kidney of partially hepatectomized animals when compared with those of sham-operated controls. The inhibition of intracellular autophagic degradation in regenerating liver has its biochemical equivalent, i.e. inhibited protein catabolism, and is interpreted as an important and adequate mechanism in effecting the shift from the physiological steady state between anabolism and catabolism to the positive balance which is required for the compensatory growth of the liver after partial hepatectomy.