The initial accumulation of carbamoylphosphate synthetase in embryonic rat hepatocytes, and the cell cycle

Roon, Marian A. van; Eier, Wilma; Charles, R.; Lamers, Wouter H.

doi:10.1111/j.1432-0436.1989.tb00741.x

Cited by 11 publications

(4 citation statements)

References 39 publications

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“…We have evaluated the possibility that local differences in cell-cycle kinetics are responsible for differences in gene expression or protein accumulation. However, the initial accumulation of CPS protein in embryonic hepatocytes was found to proceed independently of the position of the cell in the cell cycle (van Roon et al, 1989a). Thus, this finding argues against a role for the cell cycle.…”

Section: Regional Differences In the Onset Of Expression Of Carbamoylphosphatementioning

confidence: 89%

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Developmental appearance of ammonia-metabolizing enzymes in prenatal murine liver

Notenboom

Moorman

Lamers

1997

Microsc. Res. Tech.

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liver, we have investigated its expression during liver development in the mouse and compared it with that of carbamoylphosphate synthetase I (CPS). The expression of glutamate dehydrogenase was used as a marker to identify all hepatocytes in these strongly hematopoietic livers. GS protein accumulation starts in mouse hepatocytes at embryonic day (ED) 15. The first hepatocytes in which the enzyme accumulates were found around the major hepatic veins. CPS protein was found to accumulate in mouse hepatocytes from ED 13 onward: first, at the center of the median and lateral lobes, but temporarily not at the periphery of these lobes and not at the caudate lobe. The initial phase of accumulation of GS and CPS protein was characterized by a heterogeneity in enzyme content between hepatocytes. By ED 17, both enzymes were detectable in all hepatocytes at the center of the median and lateral lobes. This event marked the onset of the development of the complementary distribution of the enzymes typical of zonal heterogeneity in the adult mammalian liver. However, during the perinatal period, the pericentral hepatocytes temporarily accumulated CPS protein. We also observed heterochrony between species in the appearance of CPS protein in the small intestine.

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Section: Regional Differences In the Onset Of Expression Of Carbamoylphosphatementioning

confidence: 89%

“…However, the initial accumulation of CPS protein in embryonic hepatocytes was found to proceed independently of the position of the cell in the cell cycle (van Roon et al, 1989a). Thus, this finding argues against a role for the cell cycle.…”

Section: Regional Differences In the Onset Of Expression Of Carbamoylmentioning

confidence: 95%

Developmental appearance of ammonia-metabolizing enzymes in prenatal murine liver

Notenboom

Moorman

Lamers

1997

Microsc. Res. Tech.

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“…In such systems, the long prereplicative phase was interpreted as including the necessary time for the shift of the genetic activity from a specialized program to a more general growth-related one (Boynton and Whitfield, 1983). By contrast, in embryonic rat hepatocytes, differentiation process (accumulation of carbamoylphosphate synthetase) was found to occur in each phase of the cell cycle (van Roon et al, 1989).…”

Section: Mitogenesis and Differentiation Expression Are Separate Procmentioning

confidence: 67%

Differentiation expression during proliferative activity induced through different pathways: in situ hybridization study of thyroglobulin gene expression in thyroid epithelial cells.

Pohl

Roger

Christophe

et al. 1990

The Journal of Cell Biology

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Abstract. In canine thyrocytes in primary culture, our previous studies have identified three mitogenic agents and pathways: thyrotropin (TSH) acting through cyclic AMP (cAMP), EGF and its receptor tyrosine protein kinase, and the phorbol esters that stimulate protein kinase C. TSH enhances, while EGF and phorbol esters inhibit, the expression of differentiation. Given that growth and differentiation expression are often considered as mutually exclusive activities of the cells, it was conceivable that the differentiating action of TSH was restricted to noncycling (Go) cells, while the inhibition of the differentiation expression by EGF and phorbol esters only concerned proliferating cells.Therefore, the capacity to express the thyroglobulin (Tg) gene, the most prominent marker of differentiation in thyrocytes, was studied in proliferative cells (with insulin) and in quiescent cells (without insulin). Using cRNA in situ hybridization, we observed that TSH (and, to a lesser extent, insulin and insulin-like growth factor I) restored or maintained the expression of the Tg gene. Without these hormones, the Tg mRNA content became undetectable in most of the ceils. EGF and 12-0-tetradecanoyl phorbol-13-acetate (TPA) inhibited the Tg mRNA accumulation induced by TSH (and/or insulin). Most of the cells (up to 90%) responded to both TSH and EGE Nevertheless, the range of individual response was quite variable.The effects of TSH and EGF on differentiation expression were not dependent on insulin and can therefore be dissoc.iated from their mitogenic effects.Cell cycling did not affect the induction of Tg gene. Indeed, the same cell distribution of Tg mRNA content was observed in quiescent cells stimulated by TSH alone, or in cells ,'050 % of which had performed one mitotic cycle in response to TSH + insulin. Moreover, after proliferation in "dedifferentiating" conditions (EGF + serum + insulin), thyrocytes had acquired a fusiform fibroblast-like morphology, and responded to TSH by regaining a characteristic epithelial shape and high Tg mRNA content. 32 h after the replacement of EGF by TSH, cells in mitosis presented the same distribution of the Tg mRNA content as the rest of the cell population. This implies that cell cycling (at least 27 h, as previously shown) did not affect the induction of the Tg gene which is clearly detectable after a time lag of at least 24 h.The data unequivocally show that the reexpression of differentiation and proliferative activity are separate but fully compatible processes when induced by cAMP in thyrocytes. The inhibition of differentiation could be a side effect of the activation of the EGF and phorbol ester pathways, rather than a consequence of cell cycling itself.ULT thyroid epithelial follicular cells (thyrocytes) in primary culture keep many thyroid functions and responsiveness to various hormones, neurotransmitters, and growth factors (Lissitzky et al., 1971;Westermark et al., 1983;Roger and Dumont, 1984;Roger et al., 1982Roger et al., , 1985Errick et al., 1985; Rasp6 et al., 1986; G...

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“…Only after embryonic day 20 did the degree of methylation of site 1 decreased from approximately 80 % to 15 % at neonatal day 20. Furthermore, CbmPS expression can be readily induced by hormones in cultured embryonic day 14 hepatocytes, apparently without need for DNA replication and cell division [28,54] and, hence, dernethylation. Similarily, injection of rat fetuses with (Bt),cAMP induces phosphoenolpyruvate carboxykinase expression without apparent demethylation of the this gene, demethylation only occuring after prolonged treatment with hormones [ 5 5 ] .…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of the Rat Gene for Carbamoylphosphate Synthetase I

et al. 1995

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Carbamoylphosphate synthetase I (CbmPS) is first expressed in rat hepatocytes shortly before birth. After birth, expression of CbmPS gradually becomes confined to the hepatocytes surrounding the portal veins. To obtain insight into the spatiotemporal regulation of its expression, the rat CbmPS gene was isolated and characterized. The gene is 110kb in length and contains 38 exons. The basal promoter comprises the first 161 nucleotides upstream of the transcription‐initiation site. Determination of the state of methylation of the 5′ portion of the gene identified a CCGG sequence at ‐6.3 kb that is selectively demethylated in adult tissues which express CbmPS. This site remains methylated before birth, however, despite recruitment of all hepatocytes for CbmPS synthesis, indicating that its demethylation is a consequence of rather than a condition for expression of CbmPS. Transient expression assays revealed that the region surrounding the CCGG site at 6.3 kb functions as an enhancer. In FTO‐2B hepatoma cells and Rat‐1 fibroblasts, this enhancer is constitutively active when tested in front of the basal viral thymidine kinase promoter. When tested in front of the basal CbmPS promoter in hepatoma cells, however, the activity of this enhancer is dependent on the presence of glucocorticoids. In Rat‐1 fibroblasts, the presence of both glucocorticoids and cyclic AMP is required for full activity, suggesting that the hepatocyte‐specific expression of CbmPS is related to tissue‐specific differences in the sensitivity to cyclic AMP. Matrix‐attachment regions (MAR) are present upstream and downstream of the CbmPS gene. The downstream MAR defines the 3′ boundary of the gene. The upstream MAR is located midway between the basal promoter and the enhancer, and may function as a hinge point to facilitate the positioning of the enhancer in the vicinity of the basal promoter.

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The initial accumulation of carbamoylphosphate synthetase in embryonic rat hepatocytes, and the cell cycle

Cited by 11 publications

References 39 publications

Developmental appearance of ammonia-metabolizing enzymes in prenatal murine liver

Developmental appearance of ammonia-metabolizing enzymes in prenatal murine liver

Differentiation expression during proliferative activity induced through different pathways: in situ hybridization study of thyroglobulin gene expression in thyroid epithelial cells.

Isolation and Characterization of the Rat Gene for Carbamoylphosphate Synthetase I

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