Abstract
Ufmylation was proved to play a crucial role in hematopoietic stem cell (HSC) survival and erythroid differentiation, ufmylation deficiency induces acute anemia and lethality of embryos and adults in mouse models. To screen some compounds to rescue phenotypes induced by gene deletion, in this study, we used DDRGK1F/F; CreERT2 conditional knockout mice, DDRGK1F/F; CreERT2 bone marrow (BM) and fetal liver cells (FL), Uba5, and DDRGK1 knockdown human CD34 cell in vivo and in vitro, we found salubrinal, a novel inhibitor of eIF-2α dephosphorylation, promoted erythropoiesis at early stage, and partly rescued the acute anemia induce by DDRGK1 deficiency through upregulation of ufmylation and erythroid transcription factors. In phenylhydrazine (PHZ)-induced hemolytic anemia mice, interestingly, salubrinal could significantly improve hemocrit and red blood cell (RBC) indices of the mice treated with PHZ via upregulation of ufmylation. Its novel function was verified to attenuate unfolded protein response (UPR) and cell death programs, and to keep endoplasmic reticulum (ER) homeostasis in HSCs. Taken together results, it suggested that salubrinal may be a promising antianemic agent targeted by ufmylation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 18560-18570 |
| Number of pages | 11 |
| Journal | Journal of Cellular Physiology |
| Volume | 234 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2019 |
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Keywords
- DDRGK1
- erythropoiesis
- salubrinal
- ufmylation
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology
Cite this
Salubrinal, a novel inhibitor of eIF-2α dephosphorylation, promotes erythropoiesis at early stage targeted by ufmylation pathway. / Chen, Fanghui; Xing, Chaofeng; Zhang, Wei; Li, Jun; Hu, Tianxiang; Li, Lian; Li, Honglin; Cai, Yafei.
In: Journal of Cellular Physiology, Vol. 234, No. 10, 01.10.2019, p. 18560-18570.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Salubrinal, a novel inhibitor of eIF-2α dephosphorylation, promotes erythropoiesis at early stage targeted by ufmylation pathway
AU - Chen, Fanghui
AU - Xing, Chaofeng
AU - Zhang, Wei
AU - Li, Jun
AU - Hu, Tianxiang
AU - Li, Lian
AU - Li, Honglin
AU - Cai, Yafei
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Ufmylation was proved to play a crucial role in hematopoietic stem cell (HSC) survival and erythroid differentiation, ufmylation deficiency induces acute anemia and lethality of embryos and adults in mouse models. To screen some compounds to rescue phenotypes induced by gene deletion, in this study, we used DDRGK1F/F; CreERT2 conditional knockout mice, DDRGK1F/F; CreERT2 bone marrow (BM) and fetal liver cells (FL), Uba5, and DDRGK1 knockdown human CD34 cell in vivo and in vitro, we found salubrinal, a novel inhibitor of eIF-2α dephosphorylation, promoted erythropoiesis at early stage, and partly rescued the acute anemia induce by DDRGK1 deficiency through upregulation of ufmylation and erythroid transcription factors. In phenylhydrazine (PHZ)-induced hemolytic anemia mice, interestingly, salubrinal could significantly improve hemocrit and red blood cell (RBC) indices of the mice treated with PHZ via upregulation of ufmylation. Its novel function was verified to attenuate unfolded protein response (UPR) and cell death programs, and to keep endoplasmic reticulum (ER) homeostasis in HSCs. Taken together results, it suggested that salubrinal may be a promising antianemic agent targeted by ufmylation.
AB - Ufmylation was proved to play a crucial role in hematopoietic stem cell (HSC) survival and erythroid differentiation, ufmylation deficiency induces acute anemia and lethality of embryos and adults in mouse models. To screen some compounds to rescue phenotypes induced by gene deletion, in this study, we used DDRGK1F/F; CreERT2 conditional knockout mice, DDRGK1F/F; CreERT2 bone marrow (BM) and fetal liver cells (FL), Uba5, and DDRGK1 knockdown human CD34 cell in vivo and in vitro, we found salubrinal, a novel inhibitor of eIF-2α dephosphorylation, promoted erythropoiesis at early stage, and partly rescued the acute anemia induce by DDRGK1 deficiency through upregulation of ufmylation and erythroid transcription factors. In phenylhydrazine (PHZ)-induced hemolytic anemia mice, interestingly, salubrinal could significantly improve hemocrit and red blood cell (RBC) indices of the mice treated with PHZ via upregulation of ufmylation. Its novel function was verified to attenuate unfolded protein response (UPR) and cell death programs, and to keep endoplasmic reticulum (ER) homeostasis in HSCs. Taken together results, it suggested that salubrinal may be a promising antianemic agent targeted by ufmylation.
KW - DDRGK1
KW - erythropoiesis
KW - salubrinal
KW - ufmylation
UR - http://www.scopus.com/inward/record.url?scp=85063376657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063376657&partnerID=8YFLogxK
U2 - 10.1002/jcp.28493
DO - 10.1002/jcp.28493
M3 - Article
VL - 234
SP - 18560
EP - 18570
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 10
ER -