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Quantitative changes in the lysosomal vacuolar system of rat hepatocytes during short-term starvation

A morphometric analysis with special reference to macro and microautophagy

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Summary

Ultrastructural morphometric analysis was used to study time-dependent variations in macro and microautophagy in rat hepatocytes. Except during periods of shortterm starvation for up to 24 h, animals were kept under standardized conditions of food intake.

In hepatocytes of meal-fed rats the volume fraction of macroautophagic vacuoles is significantly higher at 23:00 h, i.e., immediately before food intake, compared to 11:00 h, i.e., 12 h following feeding. During fasting, macroautophagy drops to a low level.

Microautophagic vacuoles in hepatocytes of meal-fed rats, sacrificed at 11:00 or 23:00 h respectively, do not show any significant quantitative differences. However, during 12 h of starvation, the volume fraction of microautophagic vacuoles rises significantly, whereas the numerical density remains constant. Subsequently, during the second 12-h period of fasting, the volume fraction of microautophagic vacuoles remains unchanged, but the numerical density increases. Over a period of 24 h of starvation the volume fraction of the total lysosomal system does not change significantly, whereas the numerical density rises.

The time-dependent changes of the macroautophagic vacuolar system correlate with the circadian, food-related variations in the protein content of individual hepatocytes from meal-fed animals. The increase in volume fraction and thereafter in number of microautophagic vacuoles, as observed during starvation, coincides with a large decrease in protein content of individual hepatocytes.

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References

  • Ahlberg J, Glaumann H (1985) Uptake — microautophagy — and degradation of exogenous protein by isolated rat liver lysosomes. Effects of pH, ATP, and inhibitors of proteolysis. Exp Mol Pathol 42:78–88

    Google Scholar 

  • Ahlberg J, Marzella L, Glaumann H (1982) Uptake and degradation of proteins by isolated rat liver lysosomes. Suggestion of a microautophagic pathway of proteolysis. Lab Invest 47:523–532

    Google Scholar 

  • Amenta JS, Sargus MJ, Venkatesan S, Shinozuka H (1978) Role of the vacuolar apparatus in augmented protein degradation in cultured fibroblasts. J Cell Physiol 94:77–86

    Google Scholar 

  • Baccino FM, Tessitore L, Cecchini G, Messina M, Zuretti MF, Bonelli G, Gabriel L, Amenta JS (1982) Control of cell protein catabolism in rat liver. Biochem J 206:395–405

    Google Scholar 

  • Glaumann H, Ericsson JLE, Marzella L (1981) Mechanisms of intralysosomal degradation with special reference to autophagocytosis and heterophagocytosis of cell organelles. Int Rev Cytol 73:149–182

    Google Scholar 

  • Henell F, Glaumann H (1984) Effect of leupeptin on the autophagic vacuolar system of rat hepatocytes. Correlation between ultrastructure and degradation of membrane and cytosolic proteins. Lab Invest 51:46–56

    Google Scholar 

  • James J, Pel P, Bosch KS, Schuyt HC, Tas J (1980) Growth pattern of individual liver cells after partial hepatectomy in the rat. Eur J Cell Biol 23:137–140

    Google Scholar 

  • James J, Bosch K, Fronik G, Houtkooper J (1984) Quantitative histochemical analysis of the protein mass of hepatocytes as related to food intake. Proc R Micr Soc 19:308–309

    Google Scholar 

  • James J, Bosch KS, Fronik GM, Houtkooper JM (1985a) Naphthol-yellow-S protein content of individual hepatocytes as related to food intake and short-term starvation. Cell Tissue Res 243:165–169

    Google Scholar 

  • James J, Fronik GM, Hesseling JMG (1985b) Experiences with standardized feeding of rats with an automatic food dispensing apparatus. Lab Anim 19:255–257

    Google Scholar 

  • Kominami E, Hashida S, Khairallah EA, Katunuma N (1983) Sequestration of cytoplasmic enzymes in an autophagic vacuolelysosomal system induced by injection of leupeptin. J Biol Chem 258:6093–6100

    Google Scholar 

  • Loud AV (1968) A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J Cell Biol 37:27–46

    Google Scholar 

  • Mayahara H, Ogawa K (1972a) Heterophagy and autophagy. Int Symp Lysosomes Hakone, Abstr 52–53

  • Mayahara H, Ogawa K (1972b) Lysosomal wrapping mechanism observed in the autophagolysosome formation. In: Takeuchi T, Ogawa K, Fujita S (eds) Proc 4th Int Congr Histochem Cytochem, pp 29–30

  • McDowell EM, Trump BF (1976) Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Pathol Lab Med 100:405–414

    Google Scholar 

  • Mortimore GE, Pösö AR (1984) Lysosomal pathways in hepatic protein degradation: regulatory role of amino acids. Fed. Proc 43:1289–1294

    Google Scholar 

  • Mortimore GE, Schworer ChM (1977) Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature 270:174–176

    Google Scholar 

  • Mortimore GE, Ward WE (1981) Internalization of cytoplasmic protein by hepatic lysosomes in basal and deprivation-induced proteolytic states. J Biol Chem 256:7659–7665

    Google Scholar 

  • Mortimore GE, Hutson NJ, Surmacz CA (1983) Quantitative correlation between proteolysis and macroand microautophagy in mouse hepatocytes during starvation and refeeding. Proc Natl Acad Sci USA 80:2179–2183

    Google Scholar 

  • Ogawa K, Sakai M, Mayahara H (1984) The intracellular regulation of the lysosomal wrapping mechanism observed during autophagy. Acta Histochem [Suppl] XXX: 33–46

    Google Scholar 

  • Pfeifer U (1971) Probleme der zellulären Autophagie. Morphologische, enzymcytochemische und quantitative Untersuchungen an normalen und alterierten Leberepithelien der Ratte. Ergebn Anat Entwicklgesch 44:4

    Google Scholar 

  • Pfeifer U (1973) Cellular autophagy and cell atrophy in the rat liver during long-term starvation. A quantitative morphological study with regard to diurnal variations. Virch Arch [Cell Pathol] 12:195–211

    Google Scholar 

  • Pfeifer U (1976) Lysosomen und Autophagie. Verh Dtsch Ges Pathol 60:28–64

    Google Scholar 

  • Pfeifer U (1978) Inhibition by insulin of the formation of autophagic vacuoles in rat liver. A morphometric approach to the kinetics of intracellular degradation by autophagy. J Cell Biol 78:152–167

    Google Scholar 

  • Pfeifer U (1981) Morphological aspects of intracellular proteindegradation: autophagy. Acta Biol Med Germ 40:1619–1624

    Google Scholar 

  • Pfeifer U, Bertling J (1977) A morphometric study of the inhibition of autophagic degradation during restorative growth of liver cells in rats re-fed after starvation. Virch Arch [Cell Pathol] 24:109–120

    Google Scholar 

  • Pfeifer U, Strauss P (1981) Autophagic vacuoles in heart muscle and liver. A comparative morphometric study including circadian variations in meal-fed rats. J Mol Cell Cardiol 13:37–49

    Google Scholar 

  • Saito T, Ogawa K (1974) Lysosomal changes in rat hepatic parenchymal cells after glucagon administration. Acta Histochem Cytochem 7:1–18

    Google Scholar 

  • Schworer ChM, Mortimore GE (1979) Glucagon-induced autophagy and proteolysis in rat liver: mediation by selective deprivation of intracellular amino acids. Proc Natl Acad Sci USA 76:3169–3173

    Google Scholar 

  • Schworer ChM, Shiffer KA, Mortimore GE (1981) Quantitative relationship between autophagy and proteolysis during graded amino acid deprivation in perfused rat liver. J Biol Chem 256:7652–7658

    Google Scholar 

  • Weibel ER (1979) Stereological methods. Vol 1. Practical methods for biological morphometry. Academic Press Inc, London

    Google Scholar 

  • Weibel ER, Bolender RP (1973) Stereological techniques for electron microscopic morphometry. In: Hayat MA (ed) Principles and techniques of electron microscopy. Vol 3. Van Nostrand Reinhold Co, New York, pp 237–296

    Google Scholar 

  • Weibel ER, Gomez DM (1962) A principle for counting tissue structures on random sections. J Appl Physiol 17:343–348

    Google Scholar 

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de Waal, E.J., Vreeling-Sindelárová, H., Schellens, J.P.M. et al. Quantitative changes in the lysosomal vacuolar system of rat hepatocytes during short-term starvation. Cell Tissue Res. 243, 641–648 (1986). https://doi.org/10.1007/BF00218073

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