Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome
| Autor: | Sida Zhao, Juan Guo, Lu-Xi Song, Youshan Zhao, Chunkang Chang, Zheng Zhang, Chengming Fei, Xiao Li, Qingqing Zheng |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Erythrocytes Iron Overload Blotting Western Ros signaling Apoptosis Real-Time Polymerase Chain Reaction 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Humans Viability assay Cell damage Aged Aged 80 and over chemistry.chemical_classification Gene knockdown Reactive oxygen species Chemistry Hematology Middle Aged Hypoxia (medical) Cell cycle Flow Cytometry Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease 030104 developmental biology Oncology Myelodysplastic Syndromes 030220 oncology & carcinogenesis Immunology Cancer research Female medicine.symptom Reactive Oxygen Species Signal Transduction |
| Zdroj: | Leukemia Research. 58:55-62 |
| ISSN: | 0145-2126 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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