Article

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: 4.22). 02/2012; 227(10):3355-62. DOI: 10.1002/jcp.24071
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
107 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: NADPH oxidase 2 (NOX2) is implicated in a large number of diseases wherein inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases including Alzheimer's and Parkinson's Diseases. Herein, the evidence implicating NOX2 in normal physiology and pathophysiology is summarized. In addition, the possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will lead to increased infections and/or autoimmune disorders. Finally, the state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is summarized.
    Antioxidants & Redox Signaling 02/2014; · 8.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reactive oxygen species (ROS) can regulate diverse signaling pathways and functions in hematopoietic cells. Thioredoxin-interacting protein (TXNIP) plays an important role in mammalian cells by inhibiting thioredoxin (TRX) under oxidative stress conditions. TXNIP is expressed in hematopoietic stem cells (HSCs), and its expression decreases as HSCs differentiate into precursor cells. However, this reduction in expression does not sufficiently explain the function of TXNIP in hematopoietic cells under oxidative stress conditions. Here, we review how ROS can regulate hematopoiesis by focusing on the function of TXNIP in hematopoietic cells under oxidative stress conditions. Studies of Txnip mice have demonstrated an antioxidant function of TXNIP in hematopoietic cells or immune cells. This antioxidant function differs from the conventional pro-oxidant activity of TXNIP observed in other cell types under oxidative stress. The data suggest a context-dependent function of TXNIP under oxidative stress conditions and, in particular, a differential function of TXNIP in hematopoietic cells via its direct interaction with other redox regulatory proteins. The regulation of ROS is important in determining cellular fate decisions. TXNIP acts as a negative regulator of TRX via direct interaction, and it increases the levels of ROS under oxidative stress. However, TXNIP has an antioxidant function in hematopoietic cells or immune cells, as ROS levels are elevated and induce apoptosis in Txnip hematopoietic cells. These results suggest that the amount of TXNIP is inversely associated with ROS levels, and the loss of TXNIP can increase ROS levels in immune cells or hematopoietic cells.
    Current opinion in hematology 03/2014; · 5.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The field of redox biology has changed tremendously over the past 20 years. Formerly regarded as bi-products of the aerobic metabolism exclusively involved in tissue damage, reactive oxygen species (ROS) are now recognized as active participants of cell signaling events in health and in disease. In this sense, ROS and the more recently defined reactive nitrogen species (RNS) are, just like hormones and second messengers, acting as fundamental orchestrators of cell signaling pathways. The chemical modification of enzymes by ROS and RNS (that result in functional enzymatic alterations) accounts for a considerable fraction of the transient and persistent perturbations imposed by variations in oxidant levels. Upregulation of ROS and RNS in response to stress is a common cellular response that foments adaptation to a variety of physiologic alterations (hypoxia, hyperoxia, starvation, and cytokine production). Frequently, these are beneficial and increase the organisms' resistance against subsequent acute stress (preconditioning). Differently, the sustained ROS/RNS-dependent rerouting of signaling produces irreversible alterations in cellular functioning, often leading to pathogenic events. Thus, the duration and reversibility of protein oxidations define whether complex organisms remain "electronically" healthy. Among the 20 essential amino acids, four are particularly susceptible to oxidation: cysteine, methionine, tyrosine, and tryptophan. Here, we will critically review the mechanisms, implications, and repair systems involved in the redox modifications of these residues in proteins while analyzing well-characterized prototypic examples. Occasionally, we will discuss potential consequences of amino acid oxidation and speculate on the biologic necessity for such events in the context of adaptative redox signaling. © 2014 IUBMB Life, 2014.
    International Union of Biochemistry and Molecular Biology Life 03/2014; · 2.79 Impact Factor

Full-text

Download
10 Downloads
Available from
May 22, 2014