Sites of lipoprotein particles in normal rat hepatocytes.

Novikoff, Phyllis M.; Yam, Ana

doi:10.1083/jcb.76.1.1

Cited by 75 publications

(34 citation statements)

References 33 publications

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“…The Golgi complex shown in the present study is different from those reported in other tissues which are relatively isolated structures from each other (2,14,16,(20)(21)(22)(23)(24) : in human and mouse cultured fibroblasts the stacks of the cisternal part of the Golgi complex are relatively isolated from each other, while the continuous network of the reticular part exists as if it combines the isolated cisternal parts, thus integrating the whole Golgi complex as a single elaborate network system. Although Novikoff et al (2 1) once suggested that the GERL is a continuous structure throughout the cytoplasm, they did not show any persuasive pictures .…”

Section: Monolayer Cell Ultracytochemistrycontrasting

confidence: 54%

“…They considered the GERL the site of the formation of lysosomes of various types (2,16,19) and also of secretory granules of various kinds (20,22,23). In the present study on cultured fibroblasts, it was also suggested that the reticular part of the Golgi complex (GERL) is the site of the formation of primary lysosomes of two types, the coated vesicle type and the regular dense body type.…”

Section: Discussionmentioning

confidence: 69%

“…The Golgi complex and the "Golgi-associated smooth membrane system" (GERL) (16,21) have been intensively studied recently with ultracytochemical techniques (2,14,16,19,(20)(21)(22)(23). These studies indicated that the Golgi complex (or GERL) is not only the site of the formation of secretory granules but also the site of the formation of lysosomes of various types.…”

Section: Biological Chemistry and Genetics University Of Texasmentioning

confidence: 99%

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The Three-Dimensional Structure of the Golgi Complex in Cultured Fibroblasts. An Ultracytochemical Study With Thin and Thick Sections

Mayahara

Ishikawa

Ogawa

et al. 1978

Acta Histochem. Cytochem

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Section: Monolayer Cell Ultracytochemistrycontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 69%

Section: Biological Chemistry and Genetics University Of Texasmentioning

confidence: 99%

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The Three-Dimensional Structure of the Golgi Complex in Cultured Fibroblasts. An Ultracytochemical Study With Thin and Thick Sections

Mayahara

Ishikawa

Ogawa

et al. 1978

Acta Histochem. Cytochem

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“…Within the residual bodies, grains and other electron-opaque materials, presumably the result of intracellular digestion (9) The membrane of the lower AV2 appears compacted in areas and is therefore more electron-opaque. The possibility cannot be ruled out that the upper body labeled AV2 is a residual body derived from GERL, containing lipoprotein particles, in the manner described by Novikoff and Yam (10). The paired arrowheads indicate areas interpreted as glycogen's being internalized by microautophagy (9).…”

Section: Resultsmentioning

confidence: 99%

Endoplasmic reticulum and autophagy in rat hepatocytes.

Novikoff¹,

Shin²

1978

Proc. Natl. Acad. Sci. U.S.A.

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Electron microscopy of hepatocytes in both normal rat liver and rat liver treated to induce hyperplasia of smooth endoplasmic reticulum shows that autophagic vacuoles and residual bodies (types of lysosomes) are continuous with endoplasmic reticulum. Our laboratory has emphasized the diverse activities of GERL (1, 2) and other regions of the endoplasmic reticulum (ER) in hepatocytes (ref. 3; A. B. Novikoff, P. M. Leuenberger, P. M. Novikoff, and M. Quintana, unpublished results). In 1964 we suggested that in hepatocytes the ER is involved in forming autophagic vacuoles-lysosomes in which intracellular material is degraded: "Smooth endoplasmic reticulum appears to wrap around bits of cytoplasm, often becoming 'compacted' in the process. This may reflect an altered permeability and release of acid hydrolases and other materials to the interior of the autophagic vacuoles. The electron micrographs suggest, but do not firmly establish, that the endoplasmic reticulum thus altered becomes the delimiting membranes of the vacuoles" (ref. 4, p. 188).The growing knowledge of proteolysis in cells (reviewed in ref. 5) has revived interest in the degree to which autophagy is involved in such protein breakdown in liver. Biochemical studies on perfused rat livers, reported recently by Mortimore and his colleagues (listed in ref. 6), implicate lysosomes in the proteolysis subsequent to withdrawal of amino acids from the perfusing medium. Mortimore and Schworer (6) quantitated the "fractional cytoplasmic volumes" of the autophagic vacuoles with various constituents that rapidly develop after amino acid deprivation; the vacuoles containing glycogen were especially emphasized. The purposes of this communication are (i) to show the relation of such autophagic vacuoles to the ER in rat hepatocytes; and (ii) to present a three-dimensional model reconstructed from consecutive serial sections. MATERIALS AND METHODSSprague-Dawley rats of both sexes, 150-250 g in weight, were used for the observations on the normal rat. They were fed Purina rat chow ad lib. To induce hyperplasia of the smooth ER, we fed male Sprague-Dawley rats the Miller et al. diet (7) containing 0.06% 4-dimethylaminobenzine for 7 days, and then we partially hepatectomized the rats by the procedure of Higgins and Anderson (8). The rats were fed the 4-dimethylaminobenzine diet for an additional 5 days and then killed.The animals were anesthetized by ether, and thin slices of liver were placed into cold 1% OS04 in 0.1 M phosphate buffer containing 5% sucrose. Cubes, ca. 1 mm in each dimension, were dissected and transferred to fresh fixative. After 2 hr of fixation, the cubes were rapidly dehydrated in alcohols, treated with propylene oxide, and embedded in Epon 812. Sections, about 500-600 A thick, were cut with an LKB Ultratome and mounted on copper grids. After they were stained with lead citrate, they were examined in the Siemens Elmiskop I microscope.Serial sections were mounted on parlodion-coated single slit grids. Serial sections were prepared from four ...

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“…Kupffer cells contain high levels of lysosomal acid phosphatase, which is helpful for light and electron microscopy. 24 Cryoprotected frozen sections (10-20 m thick) were cut on a freezing microtome (Sartorious, Germany) and incubated at 37°C for 15 to 30 minutes in substrate mixture containing cytidine monophosphate (Sigma), acetate buffer, pH 5.0, and lead nitrate, as described previously. 24 After incubation, sections were rinsed in deionized water and incubated with ammonium sulfide.…”

Section: Methodsmentioning

confidence: 99%

Cyclophosphamide disrupts hepatic sinusoidal endothelium and improves transplanted cell engraftment in rat liver

et al. 2002

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To determine whether disruption of the hepatic sinusoidal endothelium will facilitate engraftment of transplanted cells, we treated Fischer 344 (F344) rats lacking dipeptidyl peptidase IV (DPPIV) activity with cyclophosphamide (CP). Electron microscopy showed endothelial injury within 6 hours following CP, and, after 24 and 48 hours, the endothelium was disrupted in most hepatic sinusoids. CP did not affect Kupffer cell function. Similarly, CP had no obvious effects on hepatocytes. Intrasplenic transplantation of F344 rat hepatocytes followed by their localization with DPPIV histochemistry showed 3-to 5-fold increases in the number of transplanted cells in CP-treated animals. Transplanted cells integrated in the liver parenchyma more rapidly in CPtreated animals, and hybrid bile canaliculi developed even 1 day after cell transplantation, which was not observed in control animals. To demonstrate whether improved cell engraftment translated into superior liver repopulation, recipient animals were conditioned with retrorsine and two-thirds partial hepatectomy (PH), which induces transplanted cell proliferation. CP treatment of these animals before cell transplantation significantly increased the number and size of transplanted cell foci. In conclusion, disruption of the hepatic sinusoidal endothelium was associated with accelerated entry and integration of transplanted cells in the liver parenchyma. These results provide insights into hepatocyte engraftment in the liver and will help in optimizing liver-directed cell therapy. ( T ransplanted hepatocytes integrate in the liver, survive throughout the life of animals, and express genes normally. 1-3 However, several days are required for transplanted cells to integrate in the liver parenchyma. 4 Moreover, transplanted cells do not proliferate significantly in the normal adult liver, 3 although, when proliferation and/or survival of native and transplanted cells are dissociated, transplanted hepatocytes can repopulate the liver extensively. [5][6][7][8][9][10] The possibility of therapeutic liver repopulation has been tested in several animal models with liver failure, genetic diseases, and metabolic deficiency states. [11][12][13][14] The swiftness with which transplanted cells engraft could be critical for liver repopulation. After injection into the portal system, transplanted cells lodge in hepatic sinusoids because of differences in the dimensions of these cells and sinusoids. 15 This is associated with changes in native hepatocytes, such as gamma-glutamyl transpeptidase activation and disruption of gap junctions. 16 The sinusoidal endothelium is disrupted 16 to 20 hours after transplantation, which provides transplanted cells access to the space of Disse. 4 Transplanted cells then translocate into the liver plate, with reconstitution of gap junctions and bile canaliculi over 3 to 7 days. However, delays in cell engraftment affect transplanted cell proliferation. In rats subjected to two-thirds partial hepatectomy (PH), which induces hepatic DNA synthesis within ...

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Sites of lipoprotein particles in normal rat hepatocytes.

Cited by 75 publications

References 33 publications

The Three-Dimensional Structure of the Golgi Complex in Cultured Fibroblasts. An Ultracytochemical Study With Thin and Thick Sections

The Three-Dimensional Structure of the Golgi Complex in Cultured Fibroblasts. An Ultracytochemical Study With Thin and Thick Sections

Endoplasmic reticulum and autophagy in rat hepatocytes.

Cyclophosphamide disrupts hepatic sinusoidal endothelium and improves transplanted cell engraftment in rat liver

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