Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy
| Autor: | María Linares, Joaquin Martinez-Lopez, Alba Rodríguez-García, Irene García-Baquero, Ricardo Sanchez, Gonzalo Carreño-Tarragona, Alicia Arenas, Teresa Cedena, José M. Bautista, Rosa Ayala, María Luz Morales, Alejandra Leivas, Vanesa Garrido-Garcia |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | 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 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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