Alteration in the regulation of plasma membrane glycoproteins of the hepatocyte during ontogeny (original) (raw)

Subcellular Morphometric and Biochemical Analyses of Developing Rat Hepatocytes

The Journal of Cell Biology, 1973

Livers of rats between the 16th gestational and 100th postnatal day of age were subjected to quantitative biochemical and electron microscope, morphometric analyses. The amount of total mitochondrial protein per gram of liver remained at 34% of the adult level throughout the last 4 days of gestation but this was the period of rapid rise in the levels of cytochrome c oxidase, aspartate aminotransferase, and glutamate dehydrogenase in mitochondria; the nuclear fraction also acquired some glutamate dehydrogenase but lost most of it during postnatal development. During early postnatal life the amount of mitochondrial protein rose in parallel with the levels of cytochrome c oxidase and glutamate dehydrogenase but the upsurges of glutaminase and, later, of ornithine aminotransferase were accompanied by relatively little change in total mitochondrial protein. The surface area of rough endoplasmic reticulum per unit volume of hepatocyte cytoplasm (SvRER) did not change significantly through...

Development of the fetal rat liver: ultrastructural and stereological study of hepatocytes

Cell differentiation, 1988

Qualitative and quantitative changes in the liver tissue composition have been studied during prenatal development of the Wistar rat by electron microscopy and stereologic methods. The absolute volume of the fetal liver is multiplied by 84 between days 13 and 20 of gestation. In the meantime, the average bepatocyte volume is multiplied by 1.5 between days 12 and 20. The volumetric fraction of hepntocytes increases from 35% of the volumetric fraction of the liver on day 12 to 66% on day 20 of gestation. The non-hepatocyte cells decrease from 49% on day 12 to 25% on day 20. By days 12 and 13, the rough endoplasmic reticulum and the Golgi apparatus are well differentiated, indicating that young fetal hepatocytes are able to synthesize and export plasma proteins. The volumetric fraction of free ribosomes decreases from 38% of the bepatocytic cytoplasm on days 12 and 13 to 6% on day 20. The mitochondrial compartment occupies about 10% of the hepatocyte cytoplasm. The mitochondria, small and round on days 12, 13 and 14, become oblong from day 18 of gestation. The shape of hepatocytes changes during the prenatal development, from potato-like on days 12, 13, 14 to cubic on day 20, with an intermediate, more spheric, stage on day 18.

A biochemical and stereological study of neonatal rat hepatocyte subpopulations

Virchows Archiv B Cell Pathology Including Molecular Pathology, 1987

Hepatocytes from 12-day-old rats, preand post-natally exposed to alcohol, together with those from pair-fed controls, were isolated and subfractionated in six cell subpopulations on Percoil density gradients. These cells were characterized using a combination of biochemical and stereological methods. The low density cells (F2) mainly showed biochemical and stereological features of perivenous hepatocytes, whereas the heavier cells (F6) were primarily periportal hepatocytes. The alcohol-metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase (high and low Km) showed more activity in the F 2 fraction. Alcohol-altered mitochondria and Golgi apparatus occurred mainly in F 2 cells, whereas the endoplasmic reticulum and lysosomes appeared to be more altered in the F6 hepatocytes. Alcohol also induced the appearance of some small hepatocytes, with a well-developed rough endoplasmic reticulum and an increased number of mitochondria. Biochemical data indicated that glutamate dehydrogenase and alanine aminotransferase were more affected in F2 cells from alcohol-treated rats, and that the activity of the ethanol-metabolizing enzymes was also reduced in these hepatocytes. Our results indicate that alcohol exposure during zonal development in the liver could have a selective effect on specific cell components depending on the acinar zone, and that the perivenous hepatocytes appear to be more damaged under these conditions.

Establishment of plasma membrane domains in hepatocytes. I. Characterization and localization to the bile canaliculus of three antigens externally oriented in the plasma membrane

The Journal of Cell Biology, 1983

A membrane fraction denoted N2 upper was isolated from homogenates of rat liver by sucrose gradient centrifugation. This fraction, which was enriched 65-fold over the homogenate in 5'-nucleotidase activity, was used as an immunogen in goats. The antisera obtained contained antibodies to three predominant polypeptides in the N2 upper membrane fraction, as shown by crossed immunoelectrophoresis. These polypeptides had molecular weights of 105,000, 110,000, and 160,000 after recovery from the crossed immunoelectrophoretic gels and are denoted PM105, PM110, and PM160. Each was a distinct polypeptide, as shown by the distinct peptide patterns resulting from limited proteolysis in the presence of detergents. The three polypeptides were synthesized by primary cultures of hepatocytes and were externally oriented at the surface of these cells, as shown by their accessibility in situ to iodination catalyzed by lactoperoxidase. They were not detectable in the serum by crossed immunoelectro...

Hepatocyte differentiation in vitro: initiation of tyrosine aminotransferase expression in cultured fetal rat hepatocytes

The Journal of Cell Biology, 1989

A fetal rat hepatocyte culture system has been used to study the molecular mechanisms of tyrosine aminotransferase (TAT) gene expression during development. It has previously been shown that TAT activity can be detected in 19-d, but not 15-d, gestation hepatocytes on the first day of culture (Yeoh, G. C. T., E A. Bennett, and I. T. Oliver. 1979. Biochem. J. 180:153-160). In this study enzyme activity, synthesis, and mRNA levels were determined in hepatocytes isolated from 13-, 15-, and 19-d gestation rats maintained in culture for 1, 2, or 3 d and exposed to dexamethasone. TAT expression is barely detectable in 13-d gestation hepatocytes even after 3 d in culture. Hepatocytes isolated from 15-d gestation fetuses have undetectable levels of enzyme activity and synthesis on the first day of culture; both can be assayed by days 2 1. Abbreviations used in this paper: GAPDH, glyceraldehyde-3-phosphatedehydrogenase; TAT, tyrosine aminotransferase.

RELATIONSHIP OF THE BIOSYNTHESIS OF ?-FETOPROTEIN, ALBUMIN, HEMOPEXIN, AND HAPTOGLOBIN TO THE GROWTH STATE OF FETAL RAT HEPATOCYTE CULTURES

Annals of the New York Academy of Sciences, 1975

a-Fetoprotein (AFP) appearance in the blood has been correlated with hepatocellular proliferation in vivo by fetal and neonatal rat l i~e r , l -~ following partial hepatectomy 4-(i and after chemically induced liver damage.', In each of these situations, blood concentrations of AFP are detectably elevated following hepatocellular division and fall when proliferation Recently, we have taken advantage of a fetal rat hepatocyte culture system to delineate the relationship between cell proliferation and the synthesis and release of AFP and albumin. This system, which was developed by one of us (H. L. L.) as a model system for the study of hepatocellular growth c o n t r 0 1 ,~-~~ obviates many technical difficulties, as well as the problems of interpretation, of in vivo experiments. The production of AFP by hepatocytes in vitro is closely coupled to transitions from quiescent to growing states, whereas albumin production occurs independently of these transitions. Preliminary studies with two additional proteins, hemopexin and haptoglobin, indicate that the relationship of hemopexin production, like that of AFP, is related to the growth state of fetal rat hepatocytes in vitro, whereas haptoglobin production, like that of albumin, is not.

Participation of hepatocytes in the production of basement membrane components in human and rat liver during the perinatal period

Cell differentiation and development : the official journal of the International Society of Developmental Biologists, 1989

Little is known about the role of the extracellular matrix in cellular growth, migration and differentiation in the developing liver. The distribution and origin of the main constituents of the hepatic extracellular matrix have never been studied during liver differentiation. We have investigated the extracellular and intracellular distribution of fibronectin, laminin and types I, III and IV collagen in both rat and human liver during the perinatal period by light and electron microscopy, using the indirect immunoperoxidase method. All these components were demonstrated extracellularly, located mainly in portal spaces and, to a lesser extent, surrounding central veins. In perisinusoidal spaces, variations in distribution were observed depending on the matrix protein, the age of the donor and the species. In fetal rat liver, fibronectin formed a continuous layer around hepatocyte clusters while laminin and type III procollagen were present in small amounts. Collagens and laminin were...

Rates of lipogenesis in fetal hepatocytes in suspension and in primary culture: hormonal effects

Biochimica Et Biophysica Acta-molecular Cell Research, 1989

utilization, but was inhibited by glucagon and noradrenaline from all substrates studied. After primary culture for 5 days in the presence of glucose, the lipogenic response to insulin increased, the glucagon response decreased and noradrenaline produced the same degree of inhibition at 3 h. At 24 h, insulin produced an even higher increase on lipogenesis parallel to an increase in fatty acid synthase activity. Dexamethasone increased lilmgenesis, but progesterone had no effect. Both hormones, in the presence of insulin, increased lipogenesis and fatty acid synthase activity. Triiodothyronine, alone or in the presence of insulin, increased iipogenesis and fatty acid synthase activity.