Sequential activation of splenic nuclear RNA polymerases by erythropoietin.

Piantadosi, Claude A.; Dickerman, Herbert W.; Spivak, Jerry L.

doi:10.1172/jci108260

Cited by 20 publications

(6 citation statements)

References 19 publications

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“…The rapidity in onset we have observed is in agreement with the times of hormonal actions mediated by cAMP as the intracellular messenger [4,8,13,16]. On the other hand, the apparent discrepancy between our results and the negative ones reported by Graber el al.…”

Section: Discussionsupporting

confidence: 91%

“…A rapid synthesis of a peculiar mRNA species, as well as the synthesis of some enzymes has been reported to occur in the ERC as early as 15-30 min following Ep administration [4,8,16]. Recently evi dence has been produced showing that Ep induces the synthesis or the release within the cytoplasm of a specific inductor (mar row cytoplasmic factor, MCF), through the interaction with membrane receptors of ERC [3].…”

Section: Introductionmentioning

confidence: 99%

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Early Increase of Cyclic Adenosine Monophosphate Level Induced by Erythropoietin on Rabbit Bone Marrow Cell Suspensions

Chiuini¹,

Torre²,

Fanò³

et al. 1979

Acta Haematol

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The effects of an erythropoietin (Ep)-rich plasma fraction and of a commercial preparation of purified Ep (Step I) on the cyclic adenosine monophosphate (cAMP) levels of suspended rabbit bone marrow cells at different incubation times (up to 10 min) were investigated. Both Ep preparations caused an early increase in cAMP concentration: using the plasma fraction a significant increase was found at the 6th, 7th, 9th and 10th min of incubation, whereas the purified Ep produces a significant increase at all incubation times, starting from 1 min. No effect was observed following incubation with fluorescein isothiocyanate (FΙTC)-inactivated Ep. These findings are discussed and a possible role of cAMP as the intracellular messenger for Ep action is suggested.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Early Increase of Cyclic Adenosine Monophosphate Level Induced by Erythropoietin on Rabbit Bone Marrow Cell Suspensions

Chiuini¹,

Torre²,

Fanò³

et al. 1979

Acta Haematol

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“…Furthermore, in some in vitro studies of this relationship, no distinction was made between changes in transcriptional activity and alterations in the net transport or pool size of RNA precursors. We, therefore, examined the in vivo effect of exogenous erythropoietin on the induction of erythropoiesis in the exhypoxic mouse spleen [108]. As summarized in Table III, the earliest effect of erythropoietin on RNA synthesis was a brief increase in nuclear RNA polymerase II activiiy which occurred within 30 minutes after injection of the hormone and well before the appearance of morphologically recognizable proerythroblasts [108].…”

Section: Zhe Biochemical Effects Of Erythropoietinmentioning

confidence: 99%

“…We, therefore, examined the in vivo effect of exogenous erythropoietin on the induction of erythropoiesis in the exhypoxic mouse spleen [108]. As summarized in Table III, the earliest effect of erythropoietin on RNA synthesis was a brief increase in nuclear RNA polymerase II activiiy which occurred within 30 minutes after injection of the hormone and well before the appearance of morphologically recognizable proerythroblasts [108]. Since injection of asialoerythropoietin failed to stimulate nuclear RNA polymerase II activity, it is unlikely that the observed effect of the erythropoietin preparation employed was due to nonspecific contaminating proteins.…”

Section: Zhe Biochemical Effects Of Erythropoietinmentioning

confidence: 99%

The mechanism of action of erythropoietin

Spivak

1986

The International Journal of Cell Cloning

172

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The proliferation and differentiation of committed erythroid progenitor cells is regulated by the glycoprotein hormone erythropoietin. Erythropoietin increases the number of developing erythroid precursors and accelerates the release of reticulocytes from the marrow without markedly altering the cell cycle length or number of mitotic divisions involved in the differentiation process. Although the hormone has been purified, molecularly cloned and sequenced, its secondary and tertiary structure and active site have not been defined. Erythropoietin has both mitogenic and differentiation functions, and whether an erythroid progenitor cell responds to the hormone by proliferating or differentiating appears to depend on its level of maturation. Erythroid progenitor cells are responsive to a variety of growth and developmental agents but only erythropoietin appears obligatory in vivo for terminal differentiation. Erythropoietin interacts with its target cells through specific high-affinity receptors and Ca*+ may be involved in the receptor-ligand interaction. Caz+ may also be involved in the induction of differentiation by erythropoietin. An increase in RNA synthesis due to activation of transcription is one of the earliest recognized effects of the hormone and appears not to require protein or DNA synthesis but the initial sequence of biochemical events triggered by erythropoietin is still undefined.are not freely accessible in the native state. Given the limited studies to date on the hormone's physical and chemical properties, it is clear that much remains to be learned about the erythropoietin molecule, particularly with respect to its structure and active site. With the availability of abundant quantities of hormone, substantial progress in this area can now be expected. m e Physiology of ErythropoiesisThe principal function of the red cell is to transport oxygen from the lungs to the tissues, and tissue oxygen demands are linked to red cell production through the action of erythropoietin. By unknown mechanisms, hypoxia stimulates erythropoietin production while a surfeit of oxygen suppresses it. Although fluctuations thus occur in the plasma erythropoietin concentration, it is worth emphasizing that such fluctuations are usually temporary and that production of the hormone is not an intermittent process. For example, while hypoxia evokes an increase in the plasma erythropoietin concentration, this soon subsides to normal even if the hypoxia persists [18, 191. Furthermore, erythrocytosis, either endogenous as in polycythemia Vera or induced by hypertransfusion, does not entirely suppress erythropoietin production [20], a phenomenon not recognized before the development of a sensitive radioimmunoassay for the hormone.Whole animal studies indicate that erythropoietin increases the number of developing erythroid precursors and accelerates the release of reticulocytes from the marrow without markedly altering the cell-cycle length or the number of mitotic divisions involved in the differentiation process [21]. In addit...

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“…In the spleen, the earliest observed effect of erythropoietin is an increase in the activity of nuclear RNA polymerase [5] which occurs within one hour after administration of the hormone. In the present study, we have employed this model in order to determine whether the activation of RNA polymerase by erythropoietin is associated with chemical modification of nuclear proteins, as suggested by Takaku et a1 [7].…”

Section: Discussionmentioning

confidence: 99%

Chemical modification of nuclear proteins by erythropoietin

Spivak

Peck

1979

American J Hematol

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The spleen of the exhypoxic polycythemic mouse was employed as a model system to study the effect of erythropoietin on enzymes that chemically modify nuclear proteins. At selected time intervals after in vivo administration of erythropoietin, acetyltransferase and methyltransferase activity were measured in nuclei isolated from the spleens of treated mice. In addition, the incorporation of labeled methyl and acetate groups into individual histone proteins was also examined. A 36% increase in nuclear acetyltransferase activity was observed eight hours after administration of erythropoietin, whereas nuclear methyltransferase activity increased by 42% 24 hours after administration of the hormone. Selective acetylation or methylation of individual histone proteins was not observed, and it is concluded that activation of transcription by erythropoietin is not the result of acetylation or methylation of nuclear proteins.

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Sequential activation of splenic nuclear RNA polymerases by erythropoietin.

Cited by 20 publications

References 19 publications

Early Increase of Cyclic Adenosine Monophosphate Level Induced by Erythropoietin on Rabbit Bone Marrow Cell Suspensions

Early Increase of Cyclic Adenosine Monophosphate Level Induced by Erythropoietin on Rabbit Bone Marrow Cell Suspensions

The mechanism of action of erythropoietin

Chemical modification of nuclear proteins by erythropoietin

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