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Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy
- Source :
- E-Prints Complutense. Archivo Institucional de la UCM, instname, Antioxidants, E-Prints Complutense: Archivo Institucional de la UCM, Universidad Complutense de Madrid, Antioxidants, Vol 8, Iss 11, p 508 (2019), Volume 8, Issue 11
- Publication Year :
- 2019
- Publisher :
- MDPI, 2019.
-
Abstract
- Control of oxidative stress in the bone marrow (BM) is key for maintaining the interplay between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an indicator of oxidative stress in the BM of patients with MDS and control subjects, and also patients with MDS under treatment with the iron chelator deferasirox (DFX). As expected, differences in the pattern of protein carbonylation were observed in BM samples between MDS patients and controls, with an increase in protein carbonylation in the former. Strikingly, patients under DFX treatment had lower levels of protein carbonylation in BM with respect to untreated patients. Proteomic analysis identified four proteins with high carbonylation levels in MDS BM cells. Finally, as oxidative stress-related signaling pathways can modulate the cell cycle through p53, we analyzed the expression of the p53 target gene p21 in BM cells, finding that it was significantly upregulated in patients with MDS and was significantly downregulated after DFX treatment. Overall, our results suggest that the fine-tuning of oxidative stress levels in the BM of patients with MDS might control malignant progression.
- Subjects :
- 0301 basic medicine
Physiology
Protein Carbonylation
Clinical Biochemistry
carbonylation
medicine.disease_cause
Biochemistry
Article
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
hemic and lymphatic diseases
oxidative stress
Medicine
Molecular Biology
business.industry
Myelodysplastic syndromes
lcsh:RM1-950
Deferasirox
Cell Biology
Microbiología médica
Cell cycle
medicine.disease
myelodysplastic syndromes
Haematopoiesis
lcsh:Therapeutics. Pharmacology
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
Bone marrow
business
deferasirox
Oxidative stress
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- E-Prints Complutense. Archivo Institucional de la UCM, instname, Antioxidants, E-Prints Complutense: Archivo Institucional de la UCM, Universidad Complutense de Madrid, Antioxidants, Vol 8, Iss 11, p 508 (2019), Volume 8, Issue 11
- Accession number :
- edsair.doi.dedup.....8f231d931754b9054ad85ab17148a3eb