TY  - JOUR
AU  - Marinković, Dragan
AU  - Zhang, Xin
AU  - Yalcin, Safak
AU  - Luciano, Julia P.
AU  - Brugnara, Carlo
AU  - Huber, Tara
AU  - Ghaffari, Saghi
PY  - 2007
UR  - http://rfasper.fasper.bg.ac.rs/handle/123456789/118
AB  - Erythroid cells accumulate hemoglobin as they mature and as a result are highly prone to oxidative damage. However, mechanisms of transcriptional control of antioxidant defense in erythroid cells have thus far been poorly characterized. We observed that animals deficient in the forkhead box O3 (Foxo3) transcription factor died rapidly when exposed to erythroid oxidative stress-induced conditions, while wild-type mice showed no decreased viability. In view of this striking finding, we investigated the potential role of Foxo3 in the regulation of ROS in erythropoiesis. Foxo3 expression, nuclear localization, and transcriptional activity were all enhanced during normal erythroid cell maturation. Foxo3-deficient erythrocytes exhibited decreased expression of ROS scavenging enzymes and had a ROS-mediated shortened lifespan and evidence of oxidative damage. Furthermore, loss of Foxo3 induced mitotic arrest in erythroid precursor cells, leading to a significant decrease in the rate of in vivo erythroid maturation. We identified ROS-mediated upregulation of P21(CIP1/WAF1/Sdi1) (also known as Cdkn1a) as a major contributor to the interference with cell cycle progression in Foxo3-deficient erythroid precursor cells. These findings establish an essential nonredundant function for Foxo3 in the regulation of oxidative stress, cell cycle, maturation, and lifespan of erythroid cells. These results may have an impact on the understanding of human disorders in which ROS play a role.
PB  - Amer Soc Clinical Investigation Inc, Ann Arbor
T2  - Journal of Clinical Investigation
T1  - Foxo3 is required for the regulation of oxidative stress in erythropoiesis
EP  - 2144
IS  - 8
SP  - 2133
VL  - 117
DO  - 10.1172/JCI31807
ER  - 

@article{
author = "Marinković, Dragan and Zhang, Xin and Yalcin, Safak and Luciano, Julia P. and Brugnara, Carlo and Huber, Tara and Ghaffari, Saghi",
year = "2007",
abstract = "Erythroid cells accumulate hemoglobin as they mature and as a result are highly prone to oxidative damage. However, mechanisms of transcriptional control of antioxidant defense in erythroid cells have thus far been poorly characterized. We observed that animals deficient in the forkhead box O3 (Foxo3) transcription factor died rapidly when exposed to erythroid oxidative stress-induced conditions, while wild-type mice showed no decreased viability. In view of this striking finding, we investigated the potential role of Foxo3 in the regulation of ROS in erythropoiesis. Foxo3 expression, nuclear localization, and transcriptional activity were all enhanced during normal erythroid cell maturation. Foxo3-deficient erythrocytes exhibited decreased expression of ROS scavenging enzymes and had a ROS-mediated shortened lifespan and evidence of oxidative damage. Furthermore, loss of Foxo3 induced mitotic arrest in erythroid precursor cells, leading to a significant decrease in the rate of in vivo erythroid maturation. We identified ROS-mediated upregulation of P21(CIP1/WAF1/Sdi1) (also known as Cdkn1a) as a major contributor to the interference with cell cycle progression in Foxo3-deficient erythroid precursor cells. These findings establish an essential nonredundant function for Foxo3 in the regulation of oxidative stress, cell cycle, maturation, and lifespan of erythroid cells. These results may have an impact on the understanding of human disorders in which ROS play a role.",
publisher = "Amer Soc Clinical Investigation Inc, Ann Arbor",
journal = "Journal of Clinical Investigation",
title = "Foxo3 is required for the regulation of oxidative stress in erythropoiesis",
pages = "2144-2133",
number = "8",
volume = "117",
doi = "10.1172/JCI31807"
}

Marinković, D., Zhang, X., Yalcin, S., Luciano, J. P., Brugnara, C., Huber, T.,& Ghaffari, S.. (2007). Foxo3 is required for the regulation of oxidative stress in erythropoiesis. in Journal of Clinical Investigation
Amer Soc Clinical Investigation Inc, Ann Arbor., 117(8), 2133-2144.
https://doi.org/10.1172/JCI31807

Marinković D, Zhang X, Yalcin S, Luciano JP, Brugnara C, Huber T, Ghaffari S. Foxo3 is required for the regulation of oxidative stress in erythropoiesis. in Journal of Clinical Investigation. 2007;117(8):2133-2144.
doi:10.1172/JCI31807 .

Marinković, Dragan, Zhang, Xin, Yalcin, Safak, Luciano, Julia P., Brugnara, Carlo, Huber, Tara, Ghaffari, Saghi, "Foxo3 is required for the regulation of oxidative stress in erythropoiesis" in Journal of Clinical Investigation, 117, no. 8 (2007):2133-2144,
https://doi.org/10.1172/JCI31807 . .