Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy

Rodríguez-García, Alba; Morales, María Luz; Garrido-García, Vanesa; García-Baquero, Irene; Leivas, Alejandra; Carreño‐Tarragona, Gonzalo; Sánchez, Ricardo; Arenas, Alicia; Cedena, María-Teresa; Ayala, Rosa; Bautista, José M.; Martínez‐López, Joaquín; Linares, María

doi:10.3390/antiox8110508

Cited by 4 publications

(7 citation statements)

References 58 publications

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“…Moreover, Hlaváčková et al identified 27 carbonylated proteins unique for MDS-RS, most of them related with the acute-phase inflammation process [40]. Consistent with these findings, an analysis of protein carbonylation in the BM of patients with MDS showed a high level of carbonylation both in myeloid series and in erythroid precursors in patients [44].…”

Section: Myelodysplastic Syndromesmentioning

confidence: 73%

“…control group [44]. Analysis of the lipid peroxidation products MDA and nitrite revealed significantly higher levels in patients with MDS and IOL compared with peers without IOL and the control group, and both parameters positively correlated with the levels of ferritin [41] (Figure 3).…”

Section: Myelodysplastic Syndromesmentioning

confidence: 89%

“…High concentrations of the HNE adduct have significant cytotoxic effects on DNA synthesis and mitochondrial activity in leukemic cells, but not in normal hematopoietic precursor cells [134]. However, a recent study examining protein carbonylation in MDS found no significant differences in HNE adducts in BM samples between the MDS and the control group [44]. Analysis of the lipid peroxidation products MDA and nitrite revealed significantly higher levels in patients with MDS and IOL compared with peers without IOL and the control group, and both parameters positively correlated with the levels of ferritin [41] (Figure 3).…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

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Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

et al. 2020

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Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and associated lipid peroxidation suppress self-renewal and induce DNA damage and genomic instability, which can trigger malignancy. A richer understanding of the clinical effects of oxidative stress might improve the prognosis of these diseases and inform therapeutic strategies. The most common protein carbonylation and lipid peroxidation compounds, including hydroxynonenal, malondialdehyde, and advanced oxidation protein products, have been investigated for their potential effect on hematopoietic cells in several studies. In this review, we focus on the most important protein carbonylation and lipid peroxidation biomarkers in hematological malignancies, their role in disease development, and potential treatment implications.

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Section: Myelodysplastic Syndromesmentioning

confidence: 73%

Section: Myelodysplastic Syndromesmentioning

confidence: 89%

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

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Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

et al. 2020

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“…Then, the measurement of protein carbonylation is performed using mass spectrophotometry, immunodetection with DNPH-specific antibodies, an ELISA assay, or immunohistochemistry. The semiquantitative detection of carbonyl content in individual proteins is assessed by one-or two-dimension electrophoresis, followed by western blot [185][186][187].…”

Section: Protein Carbonylation As An Aging Biomarkermentioning

confidence: 99%

Cellular Aging Characteristics and Their Association with Age-Related Disorders

et al. 2020

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Different molecular signaling pathways, biological processes, and intercellular communication mechanisms control longevity and are affected during cellular senescence. Recent data have suggested that organelle communication, as well as genomic and metabolic dysfunctions, contribute to this phenomenon. Oxidative stress plays a critical role by inducing structural modifications to biological molecules while affecting their function and catabolism and eventually contributing to the onset of age-related dysfunctions. In this scenario, proteins are not adequately degraded and accumulate in the cell cytoplasm as toxic aggregates, increasing cell senescence progression. In particular, carbonylation, defined as a chemical reaction that covalently and irreversibly modifies proteins with carbonyl groups, is considered to be a significant indicator of protein oxidative stress and aging. Here, we emphasize the role and dysregulation of the molecular pathways controlling cell metabolism and proteostasis, the complexity of the mechanisms that occur during aging, and their association with various age-related disorders. The last segment of the review details current knowledge on protein carbonylation as a biomarker of cellular senescence in the development of diagnostics and therapeutics for age-related dysfunctions.

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“…Finally, Rodríguez-García et al [20] studied protein carbonylation in patients with myelodysplastic syndromes. These patients had increased protein carbonyls, but levels decreased after treatment with an iron chelator (deferasirox).…”

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confidence: 99%

Free Radical Research in Cancer

Gašparović¹

2020

Antioxidants

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It can be challenging to find efficient therapy for cancer due to its biological diversity. One of the factors that contribute to its biological diversity are free radicals. Evolutionary, aerobic organisms evolve in an oxygen atmosphere, improving the energy production system by using oxygen. Oxygen is beneficial, but it can also be detrimental if free radicals are formed [1]. Free radicals, as well as some non-radical species that have oxygen, are reactive oxygen species (ROS). ROS can damage DNA leading to mutations, single, or double-strand breaks [2]. These events, if the cell is unable to repair the damage, are deleterious. If not fatal, these changes in genetic material result in tumor development by losing cell cycle control. Further, these mutations create genetic instability that result in tumor heterogeneity, and thereby increase the possibility of surviving stress conditions. In addition to direct interaction with DNA, proteins, and lipids, ROS are also signaling molecules that take an active part in regulating cellular processes [3,4]. It was previously thought that ROS only damage cells, but we now know that some enzymes primarily produce ROS, and they are not by-products [3]. These are NAD(P)H oxidases (NOX) and they produce ROS in response to inflammatory signaling. This planned production of ROS may play a role in proliferation, as ROS are able to activate signaling pathways, such as mitogen activated-protein kinase (MAPK)/extracellular-regulated kinase 1/2 (ERK1/2), phosphoinositide-3-kinase (PI3K)/protein kinase (Akt), and more, thoroughly reviewed in [3]. An important factor in surviving ROS is the antioxidant system of the cell. The main role of this complex system is to remove the excess ROS. As there are many ROS, there are many different parts of this system acting in a similar or unique way in removing ROS, such as the glutathione system, superoxide dismutase-catalase catalase, thioredoxin system, and small molecules (e.g. vitamin C, vitamin E). In order to ensure the right levels of these enzymes and small molecules, ROS activate several antioxidative transcription factors, such as Nrf2 and the FoxO family. These transcription factors are responsible for activating the majority of antioxidative genes [5][6][7]. Generally, cancer cells have increased amounts of ROS; consequently, they adapt by increasing the antioxidative defense system [8], thereby, strongly linking ROS and antioxidative research.Nevertheless, ROS were at first considered detrimental, and this was used as a therapeutic strategy in fighting cancer. Most of the conventional types of chemotherapy, as well as radiotherapy, are based on ROS production. Unfortunately, this strategy has to eradicate the tumor completely, otherwise the surviving cells adapt and build up their antioxidant systems, as well as other mechanisms (e.g., drug transporters) making themselves resistant. Strategies involving activation/inhibition of signaling pathways (and here, Nrf2 was certainly an attractive target) turned out to be a double-edged sword...

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Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy

Cited by 4 publications

References 58 publications

Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

Cellular Aging Characteristics and Their Association with Age-Related Disorders

Free Radical Research in Cancer

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