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Hepatocyte Lysosomes in Intracellular Digestion and Biliary Secretion

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Lysosomes: Background and General Considerations
1.1 Perspectives
1.2 Definitions
1.3 Characteristics
1.4 Methods of Study
2 Lysosomes: Formation and Function
2.1 Enzyme Biogenesis
2.2 Endocytosis
2.3 Functions
3 Summary
Figure 1. Figure 1.

The lysosome.

Figure 2. Figure 2.

Transmission electron microscopy of rat liver showing lysosome‐like organelle (arrowhead) in region of bile canaliculus (BC) of hepatocyte. Peroxisome (P) is also seen (x23,273).

From LaRusso 59
Figure 3. Figure 3.

Transmission electron microscopy of rat liver showing acid phosphatase reaction product in lysosome (arrowhead) in region of a bile canaliculus (BC) of hepatocyte. Mitochondria (M) and endoplasmic reticulum (ER) are also seen (X27,083).

Figure 4. Figure 4.

Transmission electron microscopy of rat liver showing secondary lysosomes (arrowheads) containing Triton WR‐1339 in vicinity of bile canaliculus (BC) (X2,857)

From LaRusso 59
Figure 5. Figure 5.

Transmission electron microscopy of rat liver showing definitive identification of lysosomes (L) by immunocytochemical demonstration of β‐galactosidase in rat hepatocytes (Panel A). AV, autophagic vacuole; BC, bile canaliculus. Note absence of reaction product in peroxisome (P), Golgi apparatus (G), and mitochondria (M). Panel B shows control section of hepatocyte exposed to nonimmune rabbit serum and absence of reaction product in lysosomes (L) (X27,234).

From Novikoff et al. 79, by copyright permission of the Rockefeller University Press
Figure 6. Figure 6.

Example of use of isopycnic centrifugation on gradient of Percoll to isolate rat liver lysosomes. In this experiment, fraction of rat liver containing predominately mitochondria and lysosomes (ML fraction) was initially prepared by homogenization and differtial centrifugation. After exposing (B) or not exposing (A) ML fraction to 1 mM CaCl2, fractions were layered on nonlinear gradient ranging in density from 1.03 to 1.13 g/ml. Marker enzymes for lysosomes (i.e., β‐glucuronidase and β‐galactosidase) and for mitochondria (i.e., malate dehydrogenase) were measured. Note that in the absence of prior exposure to CaCl2 (A), distribution in activities for all three enzymes is similar, with major peaks at density of 1.13 g/ml. After exposure to CaCl2 (B), distribution patterns for lysosomal enzymes are unchanged. In contrast, peak in activity of malate dehydrogenase has now shifted up the gradient to density of 1.05 g/ml, reflecting CaCl2‐induced osmotic swelling, and hence lightening, of mitochondria.

Figure 7. Figure 7.

Vacuolar apparatus of cell.

From LaRusso 59
Figure 8. Figure 8.

Transmission electron micrograph of bile canalicular region in liver of chronic chloroquine‐treated animal. Many of pericanalicular autophagic vacuoles (arrowheads) surrounding bile canaliculus (BC) contain concentric arrays of membranous structures. Some autophagic vacuoles occur in clusters (X9,638).

From Sewell et al. 88, copyright 1983 by The American Gastroenterological Association
Figure 9. Figure 9.

Transmission electron micrograph of liver sample from normal (A) and iron‐loaded (B) rat. Arrows indicate pericanalicular, lysosome‐like structures in normal rat liver and electron‐dense, membrane‐bound, pericanalicular organelles in iron‐loaded rat liver.

From LeSage et al. 62, by copyright permission of The American Society for Clinical Investigation
Figure 10. Figure 10.

Twenty‐four‐hour biliary excretion of acid hydrolases, total protein, and bile acids. A: β‐glucuronidase (β‐GLU), β‐galactosidase (β‐GAL), and N‐acetyl‐β‐glucosaminidase (β‐NAG) outputs are presented for each of 6 rats 1–6. B: total protein and bile acid outputs for same rats. Although excretory patterns for lysosomal enzymes varied among rats, in each rat, output patterns of the 3 lysosomal enzymes were parallel. No such parallelism existed between total protein and bile acid outputs.

From LaRusso and Fowler 60, by copyright permission of The American Society for Clinical Investigation
Figure 11. Figure 11.

Transmission electron micrograph of rat liver showing autophagic vacuole (arrowhead), a type of secondary lysosome, containing remnants of mitochondrion. Autophagic vacuole is fusing with bile canaliculus (BC) and is in the process of exocytosis (x62,500).

Figure 12. Figure 12.

Biliary output of lysosomal enzyme, N‐acetyl‐β‐glucosaminidase before and after vinblastine in bile fistula rats. Arrows indicate time at which vinblastine was given.

From Sewell et al. 89


Figure 1.

The lysosome.



Figure 2.

Transmission electron microscopy of rat liver showing lysosome‐like organelle (arrowhead) in region of bile canaliculus (BC) of hepatocyte. Peroxisome (P) is also seen (x23,273).

From LaRusso 59


Figure 3.

Transmission electron microscopy of rat liver showing acid phosphatase reaction product in lysosome (arrowhead) in region of a bile canaliculus (BC) of hepatocyte. Mitochondria (M) and endoplasmic reticulum (ER) are also seen (X27,083).



Figure 4.

Transmission electron microscopy of rat liver showing secondary lysosomes (arrowheads) containing Triton WR‐1339 in vicinity of bile canaliculus (BC) (X2,857)

From LaRusso 59


Figure 5.

Transmission electron microscopy of rat liver showing definitive identification of lysosomes (L) by immunocytochemical demonstration of β‐galactosidase in rat hepatocytes (Panel A). AV, autophagic vacuole; BC, bile canaliculus. Note absence of reaction product in peroxisome (P), Golgi apparatus (G), and mitochondria (M). Panel B shows control section of hepatocyte exposed to nonimmune rabbit serum and absence of reaction product in lysosomes (L) (X27,234).

From Novikoff et al. 79, by copyright permission of the Rockefeller University Press


Figure 6.

Example of use of isopycnic centrifugation on gradient of Percoll to isolate rat liver lysosomes. In this experiment, fraction of rat liver containing predominately mitochondria and lysosomes (ML fraction) was initially prepared by homogenization and differtial centrifugation. After exposing (B) or not exposing (A) ML fraction to 1 mM CaCl2, fractions were layered on nonlinear gradient ranging in density from 1.03 to 1.13 g/ml. Marker enzymes for lysosomes (i.e., β‐glucuronidase and β‐galactosidase) and for mitochondria (i.e., malate dehydrogenase) were measured. Note that in the absence of prior exposure to CaCl2 (A), distribution in activities for all three enzymes is similar, with major peaks at density of 1.13 g/ml. After exposure to CaCl2 (B), distribution patterns for lysosomal enzymes are unchanged. In contrast, peak in activity of malate dehydrogenase has now shifted up the gradient to density of 1.05 g/ml, reflecting CaCl2‐induced osmotic swelling, and hence lightening, of mitochondria.



Figure 7.

Vacuolar apparatus of cell.

From LaRusso 59


Figure 8.

Transmission electron micrograph of bile canalicular region in liver of chronic chloroquine‐treated animal. Many of pericanalicular autophagic vacuoles (arrowheads) surrounding bile canaliculus (BC) contain concentric arrays of membranous structures. Some autophagic vacuoles occur in clusters (X9,638).

From Sewell et al. 88, copyright 1983 by The American Gastroenterological Association


Figure 9.

Transmission electron micrograph of liver sample from normal (A) and iron‐loaded (B) rat. Arrows indicate pericanalicular, lysosome‐like structures in normal rat liver and electron‐dense, membrane‐bound, pericanalicular organelles in iron‐loaded rat liver.

From LeSage et al. 62, by copyright permission of The American Society for Clinical Investigation


Figure 10.

Twenty‐four‐hour biliary excretion of acid hydrolases, total protein, and bile acids. A: β‐glucuronidase (β‐GLU), β‐galactosidase (β‐GAL), and N‐acetyl‐β‐glucosaminidase (β‐NAG) outputs are presented for each of 6 rats 1–6. B: total protein and bile acid outputs for same rats. Although excretory patterns for lysosomal enzymes varied among rats, in each rat, output patterns of the 3 lysosomal enzymes were parallel. No such parallelism existed between total protein and bile acid outputs.

From LaRusso and Fowler 60, by copyright permission of The American Society for Clinical Investigation


Figure 11.

Transmission electron micrograph of rat liver showing autophagic vacuole (arrowhead), a type of secondary lysosome, containing remnants of mitochondrion. Autophagic vacuole is fusing with bile canaliculus (BC) and is in the process of exocytosis (x62,500).



Figure 12.

Biliary output of lysosomal enzyme, N‐acetyl‐β‐glucosaminidase before and after vinblastine in bile fistula rats. Arrows indicate time at which vinblastine was given.

From Sewell et al. 89
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Nicholas F. Larusso. Hepatocyte Lysosomes in Intracellular Digestion and Biliary Secretion. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 677-691. First published in print 1989. doi: 10.1002/cphy.cp060333