[Current data on iron overload].
Explore the source record for details and available documents.
Ferritins↗
Biomedical subjects
G Lescoat
Publications and source records attributed to G Lescoat.
Iron induction of ferritin synthesis and secretion in human hepatoma cell (Hep G2) cultures.
In order to determine if iron was able to stimulate specifically ferritin synthesis and secretion in transformed human hepatocytes in culture, human hepatoma cell (HepG2) cultures were submitted to increasing doses of ferric nitrilotriacetate. Iron uptake by the cells was demonstrated by incorporation of 59 Fe and the staining method of Perls. The following results were obtained: 1. iron incorporation within the hepatocytes increased as a function of culture time; 2. during the first 24 h of treatment, ferritin synthesis increased progressively, in parallel to the iron uptake; 3. a dose-dependent significant stimulation of ferritin synthesis and secretion were observed when the medium iron concentration increased from 5 to 20 mumol/l; 4. albumin, transthyretin and transferrin secretions were unaffected. These data demonstrated that, in our hepatocyte culture model, iron load increased the expression of ferritin in a highly specific manner.
Albumins↗
Modulation of albumin secretion by ornithine alpha-ketoglutarate in adult rat hepatocyte cultures and a human hepatoma cell line (HepG2).
Cocultured adult rat hepatocytes and a human hepatoma cell line (HepG2) were maintained in an arginine-free medium with or without ornithine alpha-ketoglutarate. This drug increased greatly hepatocyte albumin secretion in both culture models. L-Ornithine was the component accounting for these effects since similar data were obtained by using this sole amino acid. Moreover, we observed that L-ornithine stimulation of albumin production was via polyamine synthesis. Since a correlated increase in albumin mRNA was observed, it may be postulated that ornithine alpha-ketoglutarate acts at a pretranslational level.
Albumins↗
Ontogeny of secretory component in rat liver.
The ontogeny of the expression of secretory component (SC), the receptor for transepithelial transport of polymeric immunoglobulins, in the rat liver was assessed by measuring the SC concentration in liver homogenates of rats killed from birth to 60 days of age, and by quantifying the daily SC secretion of in vitro cultured hepatocytes isolated from rats similarly killed from 2 days before birth to 60 days of age. With both methodologies, only very small amounts of SC were produced by the rat liver up to 20 days of age, whereafter expression of SC markedly increased. The development of SC production in the rat liver was co-ordinate with that previously reported in the rat small intestine, preceding the appearance of large numbers of intestinal IgA plasmacytes. These data further emphasize the importance of the liver contribution, via the bile, to the intestinal secretory IgA system of the rat.
Aging↗
Effects of iron overload on transferrin secretion by cultured fetal rat hepatocytes.
Primary cultures of fetal rat hepatocytes were maintained in an arginine-free medium deprived of serum but supplemented with 0.03 mM L-ornithine and 10(-8) M dexamethasone. Ferric nitrilotriacetate was added to the culture medium in order to obtain iron concentrations ranging from 10 to 100 microM. After 24 h of treatment, iron was visualized inside the hepatocytes by the staining method of Perls and electron microscope study. The present data demonstrate that iron overload decreases transferrin secretion; this effect appears not to be specific, since albumin production is affected in a similar manner. This depressed transferrin secretion is not the consequence of hepatocyte death, as the phenomenon is confirmed when expressed per cell. Since the corresponding mRNA is unaffected, it may be postulated that iron overload decreases transferrin secretion at some post-transcriptional level.
Albumins↗
Chronic iron overload inhibits protein secretion by adult rat hepatocytes maintained in long-term primary culture.
Short-term pure cultures and long-term cocultures of adult rat hepatocytes with rat liver epithelial cells, presumably derived from primitive biliary cells, were used to define in vitro models of iron overloaded hepatocytes in order to understand the molecular mechanism responsible for liver damage occurring in patients with hemochromatosis. In vitro iron overload was obtained by daily addition of ferric nitrilotriacetate to the culture medium. A concentration of 20 microM ferric salt induced hepatocyte iron overload with minimal cytotoxicity as evaluated by cell viability, morphological changes of treated cells and cytosolic enzyme leakage into the culture medium. The effects of iron overload on protein biosynthesis and secretion were studied in both short-term pure cultures and long-term cocultures of hepatocytes. The amounts of intracellular and newly synthesized proteins were never modified by the iron treatment. Furthermore, neither the relative amounts of transferrin and albumin mRNAs nor their translational products were altered by iron overload. Moreover, no change in the transferrin isomeric forms were observed in treated cells. In contrast, a prolonged exposure of cocultured hepatocytes to 20 microM ferric salt led to a significant decrease in the amount of proteins secreted in the medium. This decrease included the two major secreted proteins, namely albumin and transferrin, and probably all other secreted proteins. These results demonstrate that iron loading alters neither the total nor the liver specific protein synthesis activity of cultured hepatocytes. They suggest that chronic overload may impede the protein secretion process.
Albumins↗
Effect of ornithine on transferrin secretion of rat and human hepatocyte cultures.
Fetal rat or neonatal human hepatocytes and a human hepatoma cell line were cultured in an arginine-free medium, supplemented or not with L-ornithine. This amino-acid improved survival of hepatocytes and strongly enhanced their transferrin secretion. Moreover, this increase observed in transferrin production was well correlated with a higher corresponding mRNA level. Thus, it may be postulated that the mechanism involved in the increased transferrin secretion by L-ornithine is of pretranslational origin.
Animals↗
Influence of ornithine on albumin synthesis by fetal and neonatal hepatocytes maintained in culture.
Fetal rat as well as fetal and neonatal human hepatocytes were cultured in an arginine-free medium with or without L-ornithine. This amino acid was found greatly to improve cell survival of both rat and human parenchymal cells and to favour their proliferation. In addition, L-ornithine appeared to modulate the expression of various functions and particularly to increase albumin secretion. Since a correlated increase of the corresponding mRNA was observed, it may be postulated that L-ornithine acts at a pre-translational level.
Albumins↗
Modulation of alpha-fetoprotein, albumin and transferrin gene expression by cellular interactions and dexamethasone in cocultures of fetal rat hepatocytes.
Fetal hepatocytes were cultured alone or in association with primitive biliary cells (RLEC) in the presence or absence of dexamethasone. Cell-cell contacts were established 3 h or five days after hepatocyte seeding and their effects on hepatocyte growth and functional activities were evaluated in the presence or absence of dexamethasone. Establishment of cellular interactions with RLEC in coculture decreased hepatocyte growth, while it stimulated production of alpha-fetoprotein, albumin and transferrin. Addition of dexamethasone to coculture inhibited alpha-fetoprotein secretion and maintained the synthesis rate of albumin and transferrin together with an additional inhibition of DNA synthesis. The levels of mRNAs corresponding to the three proteins were also measured. We observed that the levels of alpha-fetoprotein, albumin and transferrin secretion in cocultures maintained in the presence or absence of dexamethasone were well correlated with the relative amounts of their corresponding mRNAs. Consequently, it may be assumed that the primitive mechanism involved in the increased functional activity of fetal hepatocytes in coculture is of pretranslational origin. Furthermore, the present data provide evidence that heterotypic interactions and dexamethasone act as distinct modulators of growth and maturation of fetal rat hepatocytes.
Dexamethasone↗
[Iron overload of the liver and protein synthesis. Progress made through experimental models].
To understand the disturbances in protein synthesis observed during idiopathic hemochromatosis, various experimental models may be used. The aim of this research was to review the principal models employed and to demonstrate the value of hepatic tissue culture techniques in each. This method has already made it possible to explain several mechanisms involving the control of proteins in iron metabolism such as transferrin and ferritin. Tissue culture techniques of human hepatocytes should make it possible to elucidate the nature of the basic metabolic disorder in this disease responsible for the iron overload in the near future.
Animals↗
Effects of postnatal microwave exposure on thyrotropin level in the adult male rat.
Postnatal exposure of male rats to microwaves modulated the evolution of the thyrotropin level. Indeed, this treatment increased plasma TSH without affecting significantly plasma thyroxine. Moreover, the histological study of the thyroid demonstrated a high activity of this gland in irradiated animals. The modification observed in the thyrotropin level was correlated to an increase in hypothalamic noradrenaline described previously in rats submitted to the same irradiation.
Animals↗
Modulation of fetal and neonatal rat hepatocyte functional activity by glucocorticoids in co-culture.
Fetal and neonatal rat hepatocytes were cultured alone or in association with another liver epithelial cell type, in a medium with or without hydrocortisone. Secretion of albumin and alpha-fetoprotein decreased in pure hepatocyte culture, whereas in co-culture it remained stable for several days. Furthermore, addition of hydrocortisone to the co-culture medium induced a rapid increase in albumin production which was maintained at a high level. In contrast, alpha-fetoprotein production was inhibited. At the same time, an abundant extracellular material was secreted between and around hepatocyte colonies. The results demonstrate that the reciprocal relation between albumin and alpha-fetoprotein production which occurs during in vivo perinatal hepatocyte maturation is also observed in vitro. Both cell-cell contacts and glucocorticoids play a key role in this process. It appears that fetal and neonatal hepatocytes can maturate when maintained in a co-culture system.
Albumins↗
Modulation of human fetal hepatocyte survival and differentiation by interactions with a rat liver epithelial cell line.
Fetal human hepatocytes were isolated by collagenase digestion of liver fragments and cultured either alone or mixed with rat liver epithelial cells. Whereas they did not survive more than 2-3 weeks and showed rapid morphologic and functional alterations in conventional culture, fetal hepatocytes survived and retained or reverted to a globular morphology for several weeks and showed active albumin secretion for at least 13 days when cultured with rat liver cells. Increased levels of secreted albumin correlated with deposition of an insoluble extracellular material containing fibronectin and type III collagen located principally between the two cell types and around parenchymal cells. These observations show that fetal human hepatocytes are able to interact in vitro with another epithelial liver cell type obtained from a divergent species and that these cell-cell interactions influence both hepatocyte survival and expression of albumin.
Animals↗
Dynamic changes in plasma luteinizing hormone and testosterone after stress in the male rat. Influence of adrenalectomy.
In 60-day old intact male rats, stress imposed by a strange environment increased the levels of plasma LH and testosterone. Adrenalectomy, performed at 50 days of age, decreased plasma level of testosterone in basal conditions. However, without affecting the plasma level of LH significantly, stress increased plasma testosterone, albeit to a lesser extent, in the adrenalectomized rats. Stimulation of the testicular secretion by the high level of ACTH seems to be the most likely explanation for the observed testosterone peak in the adrenalectomized rat.
Adrenalectomy↗
A sex related difference in gonadotrophin response to castration in the rat.
Castration at birth, or at 25 days of age, increased plasma gonadotrophin levels in adult male and female rats. In the females, the effects of castration at 25 days of age or at birth were essentially the same. In the males castrated at 25 days of age, plasma gonadotrophin levels were less than for those castrated at birth. These results indicate a sex-related difference in the gonadotrophin response to castration.
Aging↗
Changes in plasma gonadotrophins after neurotropic stress in the postnatal castrated male rat. Influence of adrenalectomy.
In 60-day-old postnatal castrated male rat, neurotropic stress increased plasma levels of LH, FSH, ACTH, corticosterone, testosterone and 17 beta-oestradiol. The possible influence of ACTH in the observed increase in plasma sex steroids was discussed. After adrenalectomy, performed at 50 days of age, neurotropic stress no longer affected plasma gonadotrophin level significantly. Adrenalectomy, raising plasma level of corticotrophin and decreasing plasma levels of testosterone and 17 beta-oestradiol, created conditions favorable to inhibition of gonadotrophin function.
Adrenal Cortex↗
Influence of adrenalectomy on maturation of gonadotrophin function in the male rat.
The effects were studied of adrenalectomy performed at 25 days of age on the maturation of LH function and the testes during puberty (i.e. 30-50 days of age) in the male rat. In intact rats the plasma LH level increased and then decreased and the plasma testosterone level increased progressively. In adrenalectomized rats the plasma levels of LH and testosterone did not vary significantly over the same period of time. Adrenalectomy decreased the plasma levels of LH and testosterone. The different perturbations in hormonal balance induced a decrease in the size of the seminiferous tubules and a delay in spermatogenesis.
Adrenalectomy↗
[Maturation of gonadotropin and adrenocortical functions during growth of female rat].
Plasma LH, FSH and corticosterone were determined between the 15th and the 45th day of life in the normal female rat. At basal conditions plasma gonadotropins and corticosterone decreased from the 15th to the 25th day of life; then all hormones increased to the 45th day. After neurotropic stress, plasma level of corticosterone increased progressively from the 15th to the 45th day of life. It appears that the development of plasma gonadotropins and corticosterone are carried out in a parallel manner during the period studied.
Adrenal Cortex↗