REGULATION OF THE INITIATION OF HEMOGLOBIN SYNTHESIS IN THE BLOOD ISLAND CELLS OF CHICK EMBRYOS. II. EARLY ONSET AND STIMULATION OF HEMOGLOBIN FORMATION INDUCED BY EXOGENOUS δ-AMINOLEVULINIC ACID

1967 ◽  
Vol 45 (2) ◽  
pp. 344-347 ◽  
Author(s):  
S. D. Wainwright ◽  
Lillian K. Wainwright
Keyword(s):  
Early Onset ◽  
Aminolevulinic Acid ◽  
Chick Embryos ◽  
Hemoglobin Synthesis ◽  
Blood Island ◽  
Stimulation Of

REGULATION OF THE INITIATION OF HEMOGLOBIN SYNTHESIS IN THE BLOOD ISLAND CELLS OF CHICK EMBRYOS: I. QUALITATIVE STUDIES OF THE EFFECTS OF ACTINOMYCIN AND δ-AMINOLEVULINIC ACID

1966 ◽  
Vol 44 (11) ◽  
pp. 1543-1560 ◽  
Author(s):  
S. D. Wainwright ◽  
Lillian K. Wainwright
Keyword(s):  
Aminolevulinic Acid ◽  
Basal Medium ◽  
Primitive Streak ◽  
Chick Embryos ◽  
Messenger Rnas ◽  
Stages Of Development ◽  
Linear Rate ◽  
Hemoglobin Synthesis ◽  
Naked Eye ◽  
Somite Stage

Intact and de-embryonated blastodiscs of chick embryos from all stages of development between the definitive primitive streak and the 10-somite stage were incubated on simple solid synthetic media. On the basal medium, blastodiscs at all initial stages of development synthesized hemoglobin readily visible to the naked eye within 24 hours, incorporated leucine into protein at an approximately linear rate for 24 hours, and incorporated uridine into RNA at a roughly linear rate for at least 6 hours after a short lag.Blastodiscs taken before the 1-somite stage failed to synthesize any detectable hemoglobin on medium containing 2 μg/ml of actinomycin, whereas those token at later stages synthesized hemoglobin visible to the naked eye. This concentration of actinomycin totally inhibited the incorporation of uridine into high molecular weight RNA within 2–3 hours, but the incorporation of leucine into protein was not inhibited for 6–8 hours. The residual incorporation of uridine was entirely into the soluble RNA fraction.At 10 μg/ml, actinomycin markedly inhibited the synthesis of hemoglobin by blastodiscs taken at stages earlier than the 6-somite embryo, but did not markedly affect hemoglobin synthesis by the more advanced blastodiscs. This concentration of actinomycin caused only slightly greater inhibition of the incorporation of uridine into acid-precipitable material than the smaller concentration for all blastodiscs, and was not markedly more inhibitory for the incorporation of leucine into protein.The presence of δ-aminolevulinic acid overcame the inhibitions of synthesis of hemoglobin by actinomycin but did not prevent the inhibitions of incorporation of uridine into RNA and of leucine into protein.Regulation of the onset of rapid hemoglobin synthesis appears to be at the translation level, probably through the supply of δ-aminolevulinic acid. The latter is probably regulated through synthesis of RNAs formed at the head-fold stage. Messenger RNAs for globin synthesis are present at the stage of the definitive primitive streak.

REGULATION OF THE INITIATION OF HEMOGLOBIN SYNTHESIS IN THE BLOOD ISLAND CELLS OF CHICK EMBRYOS: V. QUALITATIVE STUDIES OF THE EFFECTS OF PROFLAVINE

1967 ◽  
Vol 45 (10) ◽  
pp. 1483-1493 ◽  
Author(s):  
S. D. Wainwright ◽  
Lillian K. Wainwright
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Developmental Stages ◽  
Low Molecular Weight ◽  
Chick Embryos ◽  
Hemoglobin Synthesis ◽  
Blood Island ◽  
Naked Eye ◽  
Stage Of Development ◽  
Eye Formation

Most blastodiscs explanted before the 1-somite stage of development onto medium containing 20 μg of proflavine/ml failed to form any detectable hemoglobin, whereas the majority explanted at later stages formed hemoglobin visible to the naked eye. Formation of hemoglobin by 2-somite blastodiscs was suppressed by proflavine at 50 μg/ml, but 6-somite blastodiscs formed visible quantities of hemoglobin. Incorporation of leucine into protein was inhibited by proflavine, and almost the same amount of inhibition was produced at both concentrations of inhibitor for all developmental stages examined.Net incorporation of uridine into acid-precipitable material was moderately inhibited by 20 μg of proflavine/ml, and almost totally suppressed by 50 μg of proflavine/ml. Only polynucleotides of low molecular weight accumulated in blastodiscs treated with either concentration of proflavine, but preformed stable RNA's were not degraded in the presence of inhibitor. Proflavine appeared to inhibit synthesis of, or cause degradation of, new RNA of high molecular weight at both concentrations. Accumulation of RNA of low molecular weight continued at a low proflavine concentration, but little additional RNA accumulated at a high proflavine concentration.

THE EFFECT OF THYROID HORMONE ON THE RATE OF BOTH NEUROMUSCULAR AND MUSCULAR FAILURE IN ADRENALECTOMIZED MICE MAINTAINED ON SALT

1958 ◽  
Vol 17 (2) ◽  
pp. 134-142 ◽  
Author(s):  
MARY F. LOCKETT ◽  
S. N. GANJU
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Nerve Stimulation ◽  
Early Onset ◽  
Dose Effect ◽  
Muscle Fibres ◽  
Rat Diaphragm ◽  
Direct Stimulation ◽  
Normal Rat ◽  
Stimulation Of

SUMMARY Pretreatment of salt-maintained adrenalectomized mice for 6 days with 3–6 mg dried thyroid gland, or with 0·25 μg of either l-thyroxine or l-triiodothyronine, per mouse per day, delayed the early onset of both neuromuscular and muscular failure which are characteristic of these animals. Dose-effect curves for the action of thyroxine on the myoneural junctions and striped muscle fibres are given. A concentration of 0·05μg l-triiodothyronine/100 ml. bath fluid antagonized potassium reduction of the maximal twitch of the normal rat diaphragm in response to nerve stimulation, but not in response to direct stimulation of the curarized muscle.

scholarly journals Molecular-genetic mechanisms of regulation of dihydroflavonol reductase and transcription factor Hy5 by exogenous 5-aminolevulinic acid in winter rape plants

2020 ◽  
Vol 64 (3) ◽  
pp. 317-324
Author(s):  
N. G. Averina ◽  
H. V. Yemelyanava ◽  
T. G. Kaliaha ◽  
S. M. Savina
Keyword(s):  
Transcription Factor ◽  
Light Intensity ◽  
Aminolevulinic Acid ◽  
Molecular Level ◽  
Molecular Genetic ◽  
High Light Intensity ◽  
Dependent Manner ◽  
Winter Rape ◽  
Additional Increase ◽  
Stimulation Of

The effect of exogenous 5-aminolevulinic acid (ALA) on the activity of dihydroflavonol-4-reductase (DFR), the expression of the dfr gene and the hy5 gene of the transcription factor Hy5 and the light effect of different intensities in combination with the ALA action on the accumulation of anthocyanins in cotyledonous leaves of winter rape (Brassica napus L.) were studied. It was shown that the stimulation of the accumulation of anthocyanins under the exogenous ALA action at the molecular level was provided by increasing the expression level of the dfr and hy5 genes and the activity of the DFR enzyme. Increasing the light intensity from 40.5 to 66.2 μmol photons/m2·s enhanced the ability of plants to accumulate anthocyanins on average by 35 %. The ALA action at concentrations of 50, 100, 150 and 200 mg/L led to an additional increase in the accumulation of anthocyanins at the two used levels of illumination, and in a dose-dependent manner. The stimulating effect of ALA under high light intensity was much higher than in the case of lower illumination. Thus, the stimulation of the anthocyanin accumulation under illumination of 40.5 μmol photons/m2·s was 106 % when using 50 mg/L ALA, 165 % – when using 100 mg/L ALA, 222 % – in the case of 150 mg/L ALA and 350 % – under the action of 200 mg/L ALA compared with light control without of ALA treatment. At an illumination of 66.2 μmol photons/m2·s, these indicators were 164, 262, 359 and 583 % respectively. Thus, it was demonstrated that the stimulation of the accumulation of anthocyanins under the action of ALA in winter rape plants was due to its positive effect on the transcription of the dfr and hy5 genes at the molecular level.

scholarly journals In vitro stimulation of primate hemoglobin synthesis by L-thyroxine

Blood ◽  
1977 ◽  
Vol 49 (3) ◽  
pp. 407-413 ◽  
Author(s):  
JE Fuhr ◽  
N Gengozian ◽  
M Overton
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Leucine Incorporation ◽  
Hemoglobin Synthesis ◽  
Globin Chains ◽  
Stimulation Of ◽  
Marrow Cells

Abstract Bone marrow cells from adult and abortus primates (marmosets) were incubated in vitro to determine their responsiveness to L-thyroxine. 3H- leucine incorporation into purified globin chains was the parameter assayed to determine responsiveness. Bone marrow from spontaneously aborted animals consistently was stimulated by the presence of physiologic levels of L-thyroxine. Bone marrow cells from adult animals were unaffected by the hormone.

Fam210b Is Required for Optimal Cellular and Mitochondrial Iron Uptake during Erythroid Differentiation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 405-405
Author(s):  
Yvette Y Yien ◽  
Caiyong Chen ◽  
Jiahai Shi ◽  
Liangtao Li ◽  
Daniel E. Bauer ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Aminolevulinic Acid ◽  
Genetic Modifier ◽  
Terminal Differentiation ◽  
Erythroid Differentiation ◽  
Hemoglobin Synthesis ◽  
Heme Synthesis ◽  
Mitochondrial Iron ◽  
Murine Erythroleukemia

Abstract Red cells synthesize large quantities of heme during terminal differentiation. Central to erythropoiesis is the transport and trafficking of iron within the cell. Despite the importance of iron transport during erythroid heme synthesis, the molecules involved in intracellular trafficking of iron are largely unknown. In a screen for genes that are up-regulated during erythroid terminal differentiation, we identified FAM210B, a predicted multi-pass transmembrane mitochondrial protein as an essential component of mitochondrial iron transport during erythroid differentiation. In zebrafish and mice, Fam210b mRNA is enriched in differentiating erythroid cells and liver (fetal and adult), which are tissues that require large amounts of iron for heme synthesis. Here, we report that FAM210B facilitates mitochondrial iron import during erythroid differentiation and is essential for hemoglobin synthesis. Zebrafish are anemic when fam210b is silenced using anti-sense morpholinos (Fig. A). CRISPR knockout of Fam210b caused a heme synthesis defect in differentiating Friend murine erythroleukemia (MEL) cells. PPIX levels in Fam210b deficient cells are normal, demonstrating that Fam210b does not participate in synthesis of the heme tetrapyrrole ring. Consistent with this result, supplementation of Fam210b deficient MEL cells with either aminolevulinic acid, the first committed substrate of the heme synthesis pathway or a chemical analog of protoporphyrin IX failed to chemically complement the heme synthesis defect. While Fam210b was not required for basal housekeeping heme synthesis, Fam210b deficientcells showed defective total cellular and mitochondrial iron uptake during erythroid differentiation (Fig. B). As a result, Fam210b deficient cells had defective hemoglobinization. Supplementation of Fam210b-/- MEL cells with non-transferrin iron chelates restored erythroid differentiation and hemoglobin synthesis; whereas, similar chemical complementation could not be achieved in the Tmem14c-/- cells, which have a primary defect in tetrapyrrole transport. (Fig. C). Our findings reveal that FAM210B is required for optimal mitochondrial iron import during erythroid differentiation for hemoglobin synthesis. It may therefore function as a genetic modifier for mitochondriopathies, anemias or porphyrias. Figure 1. Figure 1. Disclosures Bauer: Biogen: Research Funding; Editas Medicine: Consultancy. Orkin:Editas Inc.: Consultancy.

scholarly journals Accumulation of protoporphyrin IX from delta-aminolevulinic acid in bovine skin fibroblasts with hereditary erythropoietic protoporphyria. A gene-dosage effect.

1981 ◽  
Vol 153 (5) ◽  
pp. 1094-1101 ◽  
Author(s):  
S Sassa ◽  
S Schwartz ◽  
G Ruth
Keyword(s):  
Aminolevulinic Acid ◽  
Clinical Symptoms ◽  
Gene Dosage ◽  
Protoporphyrin Ix ◽  
Skin Fibroblasts ◽  
Erythropoietic Protoporphyria ◽  
Gene Dosage Effect ◽  
Cultured Fibroblasts ◽  
Clinically Normal ◽  
Stimulation Of

Bovine skin fibroblasts accumulated protoporphyrin IX when incubated in culture with the porphyrin-heme precursor, delta-aminolevulinic acid (ALA). Fibroblasts from cattle homozygous for erythropoietic protoporphyria (EPP) and with the clinical symptoms of the disease accumulated approximately sixfold greater amounts of protoporphyrin IX than cells from normal control animals. Cells from obligatory heterozygous animals, which are clinically normal, accumulated an intermediate level of protoporphyrin IX. When these cells were incubated with ALA and CaMg EDTA, all types of cells accumulated approximately the same amount of protoporphyrin IX (approximately 500 nmol/mg protein), suggesting that ferrochelatase activity was equally low after inhibition by treatment with CaMg EDTA in all cells. Thus the ratio of protoporphyrin IX accumulation from ALA in cultures treated with CaMg EDTA compared with controls treated with ALA alone was greatest in normal cells, least in EPP cells, and intermediate in the heterozygote cells. These findings suggest that the amount of protoporphyrin IX accumulation from ALA reflects the extent of deficiency of ferrochelatase and is proportional to the dosage of abnormal EPP gene in cultured fibroblasts. Similarly, stimulation of porphyrin accumulation by CaMg EDTA reflects diminished ferrochelatase activity in these cells. Thus, the results of this study demonstrate the usefulness of estimating protoporphyrin IX formation from ALA for the detection of an EPP gene defect in cultured bovine skin fibroblasts.

Drug-Induced Porphyrin Biosynthesis. X. Potentiation of Propanidid-Induced Elevation of δ-Aminolevulinic Acid Synthetase and Porphyrins in Chick Embryo Liver by the Carboxylesterase Inhibitor Bis-[p-nitrophenyl] Phosphate

1973 ◽  
Vol 51 (9) ◽  
pp. 700-704 ◽  
Author(s):  
Hillel Taub ◽  
G. S. Marks
Keyword(s):  
Chick Embryo ◽  
Aminolevulinic Acid ◽  
Ester Group ◽  
Synthetase Activity ◽  
Chick Embryos ◽  
Drug Induced ◽  
Duration Of Action ◽  
Nitrophenyl Phosphate ◽  
Embryo Liver ◽  
Ala Synthetase

Propanidid, an ultra short-acting non-barbiturate anesthetic containing an ester group, induces δ-aminolevulinic acid (ALA)-synthetase and porphyrin accumulation in 17-day-old chick embryo liver. The potency and duration of action of propanidid in inducing ALA-synthetase activity and porphyrin accumulation was markedly increased when administered to chick embryos which had been pretreated with bis-[p-nitrophenyl] phosphate, an inhibitor of liver carboxylesterase.

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