Increasing haemoglobin β-chain synthesis in foetal development is associated with a declining γ- to α-mRNA ratio

Kazazian, Haig H.; Silverstein, Arthur M.; Snyder, Pamela G.; Vanbeneden, Rebecca J.

doi:10.1038/260067a0

Cited by 10 publications

(6 citation statements)

References 14 publications

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“…Hormone-treated cells and controls were pooled and processed simultaneously. The amounts of radioactivity are in the same order as indicated in figure 2. and sheep fetal reticulocytes (12,13). The 0/7 ratios correspond very well with previously published results (18) and are shown in table III.…”

Section: Resultssupporting

confidence: 80%

“…We consistently found that the 7 /a ratio syn thesized was slightly higher than 1. This ap parent imbalance of globin chain synthesis is certainly not very large but is worthwhile mentioning because a preliminary report of Kazazian et al (12,13) on mRNA activities in human midterm fetuses indicates that there may be as much as two-fold excess of 7 -chain mRNA as compared with a-chain mRNA. On the contrary, the a/0 ratio reported by Shchory and Weatherall (18) in cultures of human fetal liver cells and the 7 -and a-globin mRNA activities of human fetal liver cytoplasmic RNA found by Lanyon et al (16) are lower or very close to 1.…”

Section: Discussionmentioning

confidence: 99%

“…The First and most attractive hypothesis concerning the increase of HbA synthesis without a concomitant increase in |3-chain syn thesis can be derived from the proposals of Kazazian et al (12,13) that the switch of HbF to HbA may be indirectly controlled by a decrease in the 7 /a ratio of globin chains. In this study we could not detect any changes in the 7 /a after the addition of testosterone or 17/3-estradiol to the culture cells.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Testosterone and Estradiol on Ratios of Adult to Fetal Hemoglobin in Cell Cultures of Human Fetal Liver

Congote¹,

Bruno²,

Solomon³

1977

Neonatology

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The effects of testosterone and 17β-estradiol on the synthesis of fetal and adult hemoglobins have been studied using a short-term primary cell culture system of human fetal liver at midgestation. There was a significant 23% increase in incorporation of ⁵⁹Fe into adult hemoglobin relative to the total after the addition of 5 × 10^––⁸M testosterone. 17β-Estradiol (10^––6M) lowered the incorporation of ⁵⁹Fe by 21%. β-Globin chain synthesis, measured as ³H- or ¹⁴C-leucine incorporation into globin chains, was identical in control and testosterone-treated cells and only slightly lower when 17β-estradiol was added. For this reason the observed changes in adult hemoglobin resulting from the action of testosterone and 17β-estradiol are caused by an indirect effect either in the final hemoglobin assembly or by small changes in the γ/α-chain ratio which may be undetected by the methodology used.

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Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of Testosterone and Estradiol on Ratios of Adult to Fetal Hemoglobin in Cell Cultures of Human Fetal Liver

Congote¹,

Bruno²,

Solomon³

1977

Neonatology

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“…In certain systems, control of the appearance of some proteins is pretranslational, because evidence exists suggesting that the appearance of the proteins is immediately preceded by the appearance of their respective mRNAs. Thus, the switch from fetal to adult (FA) hemoglobin in the sheep has been attributed to changes in the cellular content of functional globin mRNAs (1). Furthermore, the glucocorticoid induction of glutamine synthetase in embryonic chick neural retina cultures results from an increased rate of synthesis of the enzyme, and requires concomitant RNA synthesis (2).…”

mentioning

confidence: 99%

Developmental control of messenger RNA for hepatic tryptophan 2,3-dioxygenase

Killewich

Feigelson

1977

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

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The enzyme tryptophan 2,3-dioxygenase [EC 1.13.11.11; Ltryptophan:oxygen 2,3-oxidoreductase (decyclizing)] first appears in thelivers of young rats around the 15th postnatal day, and increases to the adult level by the 22nd day. Studies have shown that the appearance and subsequent development of the enzyme activity result from an increase in the rate of its synthesis and thus in the amount present in the liver. In this study, we have attempted to ascertain whether the appearance and development of tpto han 2,3-dioxygenase mRNA coincided with, and thus le to, e development of enzyme activity, or whether the biosynthesis of this enzyme was due to a developmental event enabling translation of a preexisting, sequestered, reservoir of its mRNA. Using a cell-free protein-synthesizing system based on a wheat germ S30 supernatant, we measured the level of tryptophan 2,3-dioxygenase mRNA in the livers of rats between 0 and 22 days of age. We found that functional tryptophan 2,3-dioxygenase mRNA is not detectable in rat liver until the 15th postnatal day. It increases to the adult level by the 22nd postnatalday, in parallel with the enzyme. The appearance and development of tryptophan 2,3-dioxygenase are the direct consequence of the parallel appearance and development of its mRNA.It has been shown that glucocorticoids, which induce tryptophan 2,3-dioxygenase activity in adult rats, are capable of inducing the appearance of this enzyme precociously in 8-and 10-day-old rats. We have found that it is also possible to induce tryptophan 2,3-dioxygenase catalytic activity with hydrocortisone precociously in 4-day-old rats. Moreover, precocious induction of enzyme activity and the induction that occurs during the enzyme's normal developmental rise to the adult level between 15 and 22 days, are mediated through parallel increases in the level of tryptophan 2,3-dioxygenase mRNA.The present findings indicate that glucocorticoids are developmental hormones that act upon the postnatal hepatocyte to evoke elevated levels of the mRNA species coding for tryptophan 2,3-dioxygenase; the findings are compatible with the hypothesis that such hormones act by initiating and accelerating transcription of the structural genes coding for the a and i protomers of this enzyme.One of the central questions in the study of development is the determination of the biochemical level at which the appearance of tissue-specific proteins is regulated. In certain systems, control of the appearance of some proteins is pretranslational, because evidence exists suggesting that the appearance of the proteins is immediately preceded by the appearance of their respective mRNAs. Thus, the switch from fetal to adult (FA) hemoglobin in the sheep has been attributed to changes in the cellular content of functional globin mRNAs (1). Furthermore, the glucocorticoid induction of glutamine synthetase in embryonic chick neural retina cultures results from an increased rate of synthesis of the enzyme, and requires concomitant RNA synthesis (2). However, in other...

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“…For example, in both humans and sheep, embryonic Hbs produced early in gestation are replaced by fetal Hb. Adult Hb subsequently replaces fetal Hb after birth (1)(2)(3)(4)(5). Sheep that are homozygous for Hb A (a2l2A) switch to the production of Hb C (a23) transiently during the neonatal period, when Hb C may be up to 35% of the total.…”

mentioning

confidence: 99%

Hemoglobin switching in sheep and goats: induction of hemoglobin C synthesis in cultures of sheep fetal erythroid cells.

Barker¹,

Pierce²,

Kefauver³

et al. 1977

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

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Synthesis of Hb F (a272) is replaced by synthesis of Hb A (a2pA) shortly before birth in sheep homozygous for the PA globin chain whereas Hb C (a2Bf2) is produced transiently during the neonatal period. We have obtained a Hb F-to-Hb C switch by generating erythroid colonies at high erythropoietin concentration in plasma clot cultures of midgestation fetal bone marrow or liver. Furthermore, high erythropoietin concentration appeared specifically to activate the gene for PC and not those for PA or OB globin in colonies grown from cells of an animal heterozygous for the PA and SB genes.Erythropoietic stress in the form of periodic bleeding or erythropoietin injection in utero did not stimulate production of Hb C (ad) hr after exposure of erythroid tissue in vitro to a high concentration of erythropoietin stimulating factor (ESF) (8, 9). A similar lag has been observed between onset of erythropoietic stress and appearance of Hb C synthesis in vivo (10). Apparently, an early erythoid stem cell responds to ESF by becoming committed with respect to the #c globin gene, and its progeny erythroid cells produce Hb C (9). Recent studies indicate that this commitment occurs approximately 24-48 hr prior to the initial accumulation of the 13C globin RNA in nuclei of early erythoid cells (11). ESF also appears to promote the development of colonies, from adult human bone marrow, that make Hb F (12, 13).In the experiments to be described, we investigated the poThe costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.tential for Hb C synthesis in fetuses known to be homozygous for the 1A globin gene. Erythroid colonies were generated in vitro from cells obtained from fetal erythroid organs, and the capacity for Hb C synthesis was analyzed. Despite the absence of Hb C production in vivo even in those fetal sheep subjected to erythropoietic stress, we obtained a Hb F-to-Hb C switch in vitro. MATERIALS AND METHODSAnimal Surgery. The mating date of sheep previously shown to be homozygous for Hb A (14) was determined by daily surveillance of breeding groups (maintained at Double J Farms, Luray, VA) for transfer of marker dye from rams to ewes. Bred ewes were removed to holding pens 72 hr later. Pregnancy was confirmed 25-35 days postcoitus by intrarectal Doppler ultrasound measurement (instrument obtained from Animark Metric, Aurora, CO). Ewes pregnant the requisite number of days were delivered to the surgical facility 24 hr preoperatively and fasted. Induction of anesthesia was accomplished with thioamylal, sodium (Surital Parke Davis, Detroit, MI) at a dose of 12.5 mg/kg intravenously. The animal was positioned in dorsal recumbency and intubated; anesthesia maintained through a semiclosed circuit with 20% nitrous oxide/2% halothane. The fetus was exposed through a midline incision and the gravid horns were approximated for access to the fetus. When tissues w...

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Increasing haemoglobin β-chain synthesis in foetal development is associated with a declining γ- to α-mRNA ratio

Cited by 10 publications

References 14 publications

Effects of Testosterone and Estradiol on Ratios of Adult to Fetal Hemoglobin in Cell Cultures of Human Fetal Liver

Effects of Testosterone and Estradiol on Ratios of Adult to Fetal Hemoglobin in Cell Cultures of Human Fetal Liver

Developmental control of messenger RNA for hepatic tryptophan 2,3-dioxygenase

Hemoglobin switching in sheep and goats: induction of hemoglobin C synthesis in cultures of sheep fetal erythroid cells.

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