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Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.
- Source :
-
Leukemia research [Leuk Res] 2017 Jul; Vol. 58, pp. 55-62. Date of Electronic Publication: 2017 Apr 23. - Publication Year :
- 2017
-
Abstract
- Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Apoptosis physiology
Blotting, Western
Female
Flow Cytometry
Humans
Iron Overload metabolism
Male
Middle Aged
Real-Time Polymerase Chain Reaction
Erythrocytes pathology
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Iron Overload complications
Myelodysplastic Syndromes complications
Reactive Oxygen Species metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5835
- Volume :
- 58
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 28460338
- Full Text :
- https://doi.org/10.1016/j.leukres.2017.04.005