Fundamental Stimulus for Erythropoiesis

During the past century, few proteins have matched erythropoietin (Epo) in capturing the imagination of physiologists, molecular biologists, and, more recently, physicians and patients. Its appeal rests on its commanding role as the premier erythroid cytokine, the elegant mechanism underlying the regulation of its gene, and its remarkable impact as a therapeutic agent, arguably the most successful drug spawned by the revolution in recombinant DNA technology. This concise review will begin with a synopsis of the colorful history of this protein, culminating in its purification and molecular cloning. It then covers in more detail the contemporary understanding of Epo's physiology as well as its structure and interaction with its receptor. A major part of this article focuses on the regulation of the Epo gene and the discovery of HIF, a transcription factor that plays a cardinal role in molecular adaptation to hypoxia. In the concluding section, a synopsis of Epo's role in disorders of red blood cell production will be followed by an assessment of the remarkable impact of Epo therapy in the treatment of anemias, as well as concerns that provide a strong impetus for the development of even safer and more effective treatment.

show abstract

“…For more detailed information on the history of Epo, see reviews by Grant and Root (1952), Erslev (1980, 1993), and Goldwasser (1996.…”

mentioning

confidence: 99%

Erythropoietin

Bunn

2013

Cold Spring Harbor Perspectives in Medicine

211

171

View full text Add to dashboard Cite

show abstract

“…One of the possible causes for the decrease in PCV as reported by many other workers (Grant & Root, 1952;Gordonet a/. 1968;Benjamin, 1978) may be testicular atrophy and degeneration, a consistent feature of Zn deficiency (Prasad & Oberleas, 1976;Mason et al 1982).…”

Section: Smentioning

confidence: 80%

“…Splenomegaly, as observed in Zn deficiency by Prasad (1980) in human patients and by Gupta (1984) in guinea-pigs, may also have attributed to this reduction since sequestration of erythrocytes in an enlarged spleen results in a fall in PCV (Hess et al 1976). Hypothyroidism as observed in the Zn-deficient guinea-pigs (Gupta, 1984) may also have played a role in the reduction in PCV values, since Morley et al (1980) reported that in rats, Zn deficiency resulted in decreased levels of triiodothyronine and thyroxine, the hormones responsible for decreased PCV (Grant & Root, 1952;Tudhope &Wilson, 1969;Benjamin, 1978). Gordon & O'Dell (1983), during 18-d experimental studies in guinea-pigs, reported that Zn deficiency had no effect on PCV.…”

Section: Smentioning

confidence: 99%

Experimental zinc deficiency in guinea-pigs: clinical signs and some haematological studies

1985

View full text Add to dashboard Cite

1. Thirty-three male, weanling guinea-pigs were divided into two groups. One group was fed on a zinc-deficient (ZnD) diet (1.25 mg Zn/kg diet) for 45 d and then divided into two subgroups: subgroup 1 continued on diet ZnD while subgroup 2 was fed on a Zn-repleted diet (100 mg Zn/kg diet) for 15 d. The second group was fed on a Zn-adequate diet (50 mg Zn/kg diet) for 60 d.2. Zn deficiency could be produced within 21 d as evidenced by clinical signs and reduction in serum Zn concentration.3. Clinical signs exhibited were listlessness, scabby lesions on skin near the foot pads, mild alopecia and a reduction in body-weight gain. No effect was observed on food intake.4. Significant decreases in packed cell volume and total leucocyte count from 48 d onwards accompanied by absolute lymphocytopenia and relative neutrophilia were observed.5. Supplementation of Zn in the Zn-repleted group resulted in marked, though incomplete, improvement with regard to serum Zn concentration, clinical signs and haematological changes.

show abstract

“…Third, de novo synthesis of red blood cells, erythropoiesis, is increased. The fundamental stimulus for erythropoiesis is the ratio between oxygen consumed and oxygen delivered (38). Although various effectors can affect erythrocyte production, the most important single substance is erythropoietin, a hormone largely produced in the kidney (49).…”

Section: Circulatory Rearrangementsmentioning

confidence: 99%

Natriuretic peptides in hormonal regulation of hypoxia responses

Arjamaa¹,

Nikinmaa²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

The possibility that natriuretic peptides' effects are important in hypoxia responses of vertebrates is reviewed. Both the transcription and release of natriuretic peptides are affected by oxygen tension. Furthermore, many of the effects observed in hypoxia, such as diuresis and a reduction of plasma volume, are also caused by treatment of the animal with natriuretic peptides. Also, several clinical observations about changes in natriuretic peptide levels in, e.g., sleep apnea and cyanotic congenital heart disease, are consistent with the idea that hypoxia is involved in the etiology of conditions, in which natriuretic peptide levels increase. Virtually all published information on the relationship between oxygen and natriuretic peptides is based on human studies. Because hypoxic conditions are more common in aquatic than terrestrial environments, future studies about the possible role of natriuretic peptides in hypoxia, as well as the role of hypoxia in the evolution of natriuretic peptides, including the different subtypes, should increasingly involve also aquatic organisms.low oxygen tension; cardiac hormones; mammals; fishes THE ROLE OF NATRIURETIC PEPTIDES in ion and water regulation has been repeatedly reviewed both in mammalian (e.g., 75, 82, 112) and comparative vertebrate (51, 92) systems after their discovery in the early 1980s. Because the findings on the natriuretic peptides cannot all be accommodated with the osmoregulatory actions of the hormones in fish, Farrell and Olson (32) have formulated a cardioprotective hypothesis to explain the role for these hormones. The osmoregulatory and cardioprotective hypotheses account for many natriuretic peptide effects. However, even after the many thousand investigations on natriuretic peptides, predominantly in terrestrial mammals, their physiological role(s) remain somewhat unclear (51, 77). The present contribution reviews the possibility that natriuretic peptide function is an important response to hypoxia in vertebrates. Earlier, Chen (18) has reviewed ANP function in hypoxia. Because the vast majority of studies have been performed in man and other mammals, this contribution also focuses on them. However, information and hypotheses relevant for other vertebrate groups are presented whenever possible.There is a significant analogy between the natriuretic peptide system and the adrenergic system, which responds to hypoxic conditions, in many ways. Natriuretic peptides (41) adrenaline and noradrenaline are stored in large concentrations in secretory granules of the cells where they are produced and can be rapidly secreted into circulation. The largely systemic adrenergic responses are immediate ("fight or flight response"), maximizing oxygen transport and energy usage in the short term. Circulating catecholamines are rapidly broken down, as are natriuretic peptides (48,114). Notably, catecholamines play an important role in hypoxia responses of animals: they maximize oxygen transport by causing the release of erythrocytes from storage organs (72) and increa...

show abstract

Fundamental Stimulus for Erythropoiesis

Cited by 130 publications

References 0 publications

Erythropoietin

Erythropoietin

Experimental zinc deficiency in guinea-pigs: clinical signs and some haematological studies

Natriuretic peptides in hormonal regulation of hypoxia responses

Contact Info

Product

Resources

About