# Selenium, Selenoproteins, and Stress Erythropoiesis

> **NIH NIH R01** · PENNSYLVANIA STATE UNIVERSITY, THE · 2021 · $305,310

## Abstract

Selenium (Se) functions as a redox gatekeeper through its incorporation as selenocysteine (Sec) in
selenoproteins. This co-translational process is highly regulated by Sec insertion sequence (SECIS) in the 3’
UTR of mRNA, which allows the tRNA[Sec] (encoded by Trsp), to recognize a UGA stop codon and insert Sec
into the growing polypeptide chain. Erythropoiesis presents a particular problem to redox regulation as the
presence of iron, heme, and unpaired globin chains can lead to high levels of free radical-mediated oxidative
stress, which are detrimental to erythroid development and can lead to anemia. Under homeostatic conditions,
bone marrow erythropoiesis produces sufficient erythrocytes to maintain homeostasis. In contrast, anemic stress
induces an alternative pathway, stress erythropoiesis, which rapidly produces new erythrocytes to alleviate the
anemia. In line with their antioxidant, anticancer, and anti-inflammatory functions, selenoproteins protect
erythrocytes from oxidative damage, while their absence causes hemolysis of erythrocytes due to oxidative
stress. We have recently demonstrated that Se deficiency or lack of selenoproteins severely impaired stress
erythropoiesis exacerbating anemia. These data support observations in patients where low serum Se is
associated with increased risk of anemia in the elderly. Similarly, sickle cell anemia (SCA) patients present with
significantly lower serum Se and glutathione peroxidase (GPX) activity suggesting that impaired erythrocyte
stability and defective erythropoietic response may in part result from a decreased antioxidant potential to
effectively metabolize pro-oxidant species. Macrophages play a key role in erythropoiesis. Erythroid progenitors
develop in close proximity with macrophages in structures referred to as erythroblastic islands (EBIs). Se
deficiency or lack of selenoproteins impairs the development of EBIs in the splenic niche and compromises the
recovery from anemia. These data suggest that selenoproteins are critical in both the progenitors and the
microenvironment to regulate stress erythropoiesis. The proposed studies are based on the hypothesis that
Se, through selenoproteins, plays a key role in supporting effective stress erythropoiesis and erythroid
development to enable recovery from anemia by affecting both stress erythroid progenitors (SEPs) and
the erythropoietic niche that contains macrophages. The hypothesis will be tested using a bone marrow
transplant model of anemia along with other secondary acute anemia models in the following specific aims: 1)
Examine the role of SelenoW in erythroid differentiation during acute anemia; 2) Dissect the role of
selenoproteins in monocytes/macrophages in the establishment of EBIs during stress erythropoiesis; 3) Examine
the role of selenoproteins in the regulation of the proliferation and differentiation of SEPs. Successful completion
of this proposal will increase our understanding of how selenoproteins regulate stress erythr...

## Key facts

- **NIH application ID:** 10197916
- **Project number:** 5R01DK119865-03
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** ROBERT Frank PAULSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $305,310
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197916

## Citation

> US National Institutes of Health, RePORTER application 10197916, Selenium, Selenoproteins, and Stress Erythropoiesis (5R01DK119865-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10197916. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*