Intercellular communication in normal and regenerating rat liver: a quantitative analysis.

Meyer, David J.; Yancey, S B; Revel, Jean‐Paul

doi:10.1083/jcb.91.2.505

Cited by 135 publications

(58 citation statements)

References 47 publications

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“…There is ample evidence that, in regenerating liver, contact between hepatocytes is loosened (25)(26)(27) as discussed before (6). If impairment of the regulatory mechanism persists, the hepgtocytes may remain continuously in the cell cycle, and in this state they may be transformed and lose their response to the cell-surface modulator.…”

Section: Discussionmentioning

confidence: 99%

Loss of reciprocal modulations of growth and liver function of hepatoma cells in culture by contact with cells or cell membranes.

Nakamura¹,

Nakayama²,

Teramoto³

et al. 1984

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

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In mature rat hepatocytes in primary culture, many metabolic functions and cell growth are controlled reciprocally by cell density, and this reciprocal regulation is mediated by a cell-surface modulator through cell-cell contact. Cultured RY-121B cells from Reuber hepatoma and MH1Cj cells from Morris hepatoma, which retain some liverspecific functions, did not show any cell-density dependency of either cell growth or hepatocyte-specific functions, such as induction of tyrosine aminotransferase by dexamethasone. However, when RY-121B cells were cocultured with a low density of rat hepatocytes as monolayers in direct contact, they exerted contact-dependent control of DNA synthesis and of differentiated function of the hepatocytes. Furthermore, plasma membranes from various tumor cells including these hepatoma cells had strong modulator activity on primary cultures of normal rat hepatocytes, and their activity mimicked the reciprocal effects of cell density on DNA synthesis and induction of tyrosine aminotransferase. On the contrary, addition of plasma membranes from normal adult rat liver to sparse cultures of RY-121B or MH1Cj cells did not cause any inhibition of active DNA synthesis or enhancement of induction of tyrosine aminotransferase in these cells. These results suggest that hepatoma cells have lost cell density-dependent regulations of many cellular activities and cell growth because they have lost the ability to respond to the cell surface modulator, although they retain modulator activity on their plasma membranes.

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Section: Discussionmentioning

confidence: 99%

Loss of reciprocal modulations of growth and liver function of hepatoma cells in culture by contact with cells or cell membranes.

Nakamura¹,

Nakayama²,

Teramoto³

et al. 1984

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

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“…In liver regeneration there is swelling of liver lobules and disappearance of gap junctions morphologically and decreased transfer of substances of low molecular weight and of electrical coupling functionally (36,37). Liver tissue consists of not only parenchymal hepatocytes but also other cells, such as cells of the bile ducts, endothelium, and connective tissues.…”

Section: Effects Of Cell Density On Various Metabolic Activities Ofmentioning

confidence: 99%

Reciprocal modulation of growth and differentiated functions of mature rat hepatocytes in primary culture by cell--cell contact and cell membranes.

Nakamura¹,

Yoshimoto²,

Nakayama³

et al. 1983

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

241

109

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In primary monolayer cultures of rat mature hepatocytes, many metabolic functions as well as cell growth are regulated by cell density. There are two types of regulatory response of these functions to change of cell density. Growth-related functions, such as DNA synthesis, induction of glucose-6-phosphate dehydrogenase, 2-aminoisebutyric acid transport, synthesis of cellular protein, and cholesterogenesis, are stimulated by low cell density. In contrast, functions related to hepatocyte-specific characters, such as the inductions of tyrosine aminotransferase, serine dehydratase, and malic enzyme and synthesis of triglycerides, are stimulated by high cell density. The reciprocal responses of these cellular activities to cell density were mimicked by addition of plasma membranes purified from adult rat liver to hepatocytes cultured at low cell density. The modulator activity was heat labile and trypsin sensitive. The activity was also found in plasma membranes from kidney, brain, and erythrocytes, although the specific activities of these preparations seemed to be different. These results suggest that the reciprocal regulations of cell growth and hepatocyte-specific functions are mediated by some surface components via cell-cell contact.Adult rat hepatocytes in primary culture retain in vivo levels of various liver functions and respond to various hormones (1)(2)(3)(4) Cell Isolation and Monolayer Culture. Parenchymal hepatocytes were isolated from male Wistar rats weighing 150-200 g by in-situ perfusion on the liver with collagenase, essentially as described by Seglen (11). The isolated cells were suspended at 5 X 10' cells per ml in Williams medium E containing 2% calf serum and 2 nM insulin. The cell density at inoculation was varied from 5 X 105 to 2.5 x 106 cells per 5-cm (diameter)Corning plastic culture dish. Over 80% of the cells became attached in 1 hr at 37C under 5% C02/30% 02 in air. After culture for 2 hr. the medium -was changed to hormone-free Williams medium E containing 5% calf serum. In experiments on the effect of addition of plasma membranes, rat hepatocytes were inoculated at a low density (7 x 105 cells per 5-cm dish). After 2 hr. the medium was changed to hormone-free medium containing 5% calf serum and then various amounts of plasma membranes were added to the cultures. Hormones were added to the medium after 22 hr of culture. Incubation was continued for 24 or 45 hr further and then various activities were assayed.Assay of DNA Synthesis. DNA synthesis was assayed by measuring incorporation of [3H]thymidine into DNA with or without hydroxyurea in 2 hr. Radioactivity in the hot trichloroacetic acid-soluble fraction was measured as described (6). Assays of Enzyme Activities. The cells were harvested with a rubber policeman in 0.2-1.0 ml of 20 mM potassium phosphate buffer (pH 7.5) containing 0.1 mM dithiothreitol and 5 mM EDTA for the glucose-6-phosphate dehydrogenase (Glc-6-P-DHase) assay, in 0.1-0.5 ml of 5 mM Tris-HCl buffer (pH

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“…Previously, function of gap junctions (GJ) has been evaluated based on the distribution of fluorescent dyes after the microinjection into the cultured tissues and cells (Jongen et al 1991, Meyer et al 1981. Therefore, we evaluated the distribution of LY dye in the respective intralobular zones.…”

Section: Fig 5 Serial Changes In the Bile Canalicular Fluorescence (mentioning

confidence: 99%

Three‐dimensional visualization and physiologic evaluation of bile canaliculi in the rat liver slice by confocal laser scanning microscopy

Yoneyama

2001

Scanning

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Summary:We evaluated the morphology and physiologic function of the bile canaliculi (BC) in the rat liver slice (RLS) by confocal laser scanning microscopy (CLSM). Lucifer yellow (LY) dye was injected into the RLS, and the distribution of LY was serially evaluated. After the injection of LY, hepatocytes were initially visualized, followed by visualization of the BC. There was no significant difference in the distribution of LY between zones 1 and 3 in the hepatic lobule. In zone 1, the reticular distribution of the BC was observed, whereas the part of BC was linearly visualized in zone 3 along the course of sinusoids. When changes in the bile canalicular fluorescence (BCF) were serially evaluated, the BCF was decreased to the minimal level (88% of the value obtained immediately after the LY injection) 10 min after the LY injection, and it tended to increase thereafter. The intralobular hepatocyte fluorescence (ILHF) was decreased to 58.9% of the initial value during the first 40 min. However, the ILHF was transiently increased 30 min after the LY injection, suggesting the possibility of reabsorption of LY by hepatocytes. Three-dimensional (3-D) reconstruction images of the BC facilitated the evaluation of the stereoscopic structure of BC. Confocal laser scanning microscopy facilitated the evaluation of structures and physiologic function of the BC.

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Intercellular communication in normal and regenerating rat liver: a quantitative analysis.

Cited by 135 publications

References 47 publications

Loss of reciprocal modulations of growth and liver function of hepatoma cells in culture by contact with cells or cell membranes.

Loss of reciprocal modulations of growth and liver function of hepatoma cells in culture by contact with cells or cell membranes.

Reciprocal modulation of growth and differentiated functions of mature rat hepatocytes in primary culture by cell--cell contact and cell membranes.

Three‐dimensional visualization and physiologic evaluation of bile canaliculi in the rat liver slice by confocal laser scanning microscopy

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