Oxidases and reactive oxygen species during hematopoiesis: A focus on megakaryocytes

Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Journal of Cellular Physiology (Impact Factor: 3.84). 10/2012; 227(10):3355-62. DOI: 10.1002/jcp.24071
Source: PubMed


Reactive oxygen species (ROS), generated as a result of various reactions, control an array of cellular processes. The role of ROS during megakaryocyte (MK) development has been a subject of interest and research. The bone marrow niche is a site of MK differentiation and maturation. In this environment, a gradient of oxygen tension, from normoxia to hypoxia results in different levels of ROS, impacting cellular physiology. This article provides an overview of major sources of ROS, their implication in different signaling pathways, and their effect on cellular physiology, with a focus on megakaryopoiesis. The importance of ROS-generating oxidases in MK biology and pathology, including myelofibrosis, is also described.

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Available from: Shinobu Matsuura, May 22, 2014
    • "SOD acts as the first line of defense by converting the superoxide free radical to hydrogen peroxide. Hydrogen peroxide is further broken down by catalase to oxygen and water (Powers et al. 2011; Eliades, Matsuura & Ravid 2012). Glutathione peroxidase also assists with this process and converts hydrogen peroxide to water (Kerksick & Willoughby 2005). "
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    ABSTRACT: 1.The interaction between UV-B and temperature can modify the effects of climate variability on animal function because UV-B and increasing temperatures may increase reactive oxygen species (ROS) production and thereby impair animal performance. However, antioxidant enzyme activities are also increased at higher temperatures, which could counteract negative effects of increased ROS. Conversely, UV-B exposure at lower temperature can exacerbate the effects of ROS because of lower antioxidant enzyme activities.2.Phenotypes can be plastic to compensate for potentially negative environmental effects. Plasticity may be induced by conditions experienced during pre- or early post-zygotic development, and it may occur reversibly within adult organisms (acclimation). Developmental plasticity and acclimation may interact to determine phenotypes in variable environments.3.Here we tested the hypothesis that increased antioxidant enzyme activities are insufficient to alleviate the interactive effects of UV-B and increased temperature on mosquitofish (Gambusia holbrooki). Additionally, we tested whether developmental conditions influenced the capacity for acclimation to UV-B and temperature so that cohorts born in summer at high UV-B and temperature conditions are better able to compensate for ROS damage compared to cohorts born in winter.4.We exposed mosquitofish to UV-B and control (no-UV-B) at different acclimation temperatures (18, 28 and, 32o C), and measured responses acutely at 18, 28 and, 32o C in a fully factorial design. In fish born in summer, UV-B had significant negative effects on swimming performance and resting metabolic rate at both low (18o C) and high (32o C) acclimation temperatures, which were accompanied by higher ROS-induced damage. At their average temperature experienced naturally (28o C), fish born in summer were not affected by UV-B and showed lower damage and higher antioxidant enzyme activities compared to the other acclimation temperatures. In contrast, swimming performance of winter-caught fish was negatively affected by UV-B at all acclimation temperatures, which was paralleled by higher ROS-induced damage and antioxidant enzyme activities that did not acclimate. However, metabolic scope was not reduced by UV-B or temperature in any of the cohorts.5.Our results showed that developmental conditions modify the capacity for acclimation later in life, and that the interaction between developmental and acclimation conditions can increase the resilience of animals to environmental variability. These results have important implications for understanding the evolution of acclimation, and for predictions of how climate change affects animal performance.This article is protected by copyright. All rights reserved.
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    • "ROS generation is involved in LPA 3 -mediated MK differentiation Since β-catenin was identified as a mediator of LPA 2 signaling, we further explored the possible downstream of LPA 3 that may involve in megakaryopoiesis. It has been reported that ROS play essential roles in MK maturation [44]. Our previous study on LPA established a model that LPA 3 activates phospholipase-C (PLC), PKC-δ and the ROS signaling cascades, to enhance vascular endothelial growth factor C (VEGF-C) expression in prostate cancer cells [45] [46]. "

    Full-text · Article · May 2015 · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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    ABSTRACT: The human myelogenous cell line, K562 has been extensively used as a model for the study of megakaryocytic (MK) differentiation, which could be achieved by exposure to phorbol 12-myristate 13-acetate (PMA). In this study, real-time PCR analysis revealed that the expression of catalase (cat) was significantly repressed during MK differentiation of K562 cells induced by PMA. In addition, PMA increased the intracellular reactive oxygen species (ROS) concentration, suggesting that ROS was a key factor for PMA-induced differentiation. PMA-differentiated K562 cells were exposed to hydrogen peroxide (H2O2) to clarify the function of ROS during MK differentiation. Interestingly, the percentage of high-ploidy (DNA content >4N) cells with H2O2 was 34.8±2.3% at day 9, and was 70% larger than that without H2O2 (21.5±0.8%). Further, H2O2 addition during the first 3 days of PMA-induced MK differentiation had the greatest effect on polyploidization. In an effort to elucidate the mechanisms of enhanced polyploidization by H2O2, the BrdU assay clearly indicated that H2O2 suppressed the division of 4N cells into 2N cells, followed by the increased polyploidization of K562 cells. These findings suggest that the enhancement in polyploidization mediated by H2O2 is due to synergistic inhibition of cytokinesis with PMA. Although H2O2 did not increase ploidy during the MK differentiation of primary cells, we clearly observed that cat expression was repressed in both immature and mature primary MK cells, and that treatment with the antioxidant N-acetylcysteine effectively blocked and/or delayed the polyploidization of immature MK cells. Together, these findings suggest that MK cells are more sensitive to ROS levels during earlier stages of maturation.
    No preview · Article · Jun 2013 · Experimental Cell Research
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