Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and produce constitutively reactive oxygen species

Piccoli, Cláudia; D’Aprile, Annamaria; Ripoli, Maria; Scrima, Rosella; Lecce, Lucia; Boffoli, Domenico; Tabilio, Antonio; Capitanio, Nazzareno

doi:10.1016/j.bbrc.2006.12.148

Cited by 130 publications

(122 citation statements)

References 33 publications

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“…It would also be interesting to analyse whether different haematopoietic cytokines function through specific NADPH oxidases. In this sense, it is known that HSCs express different Nox family members, 26 whose particular roles are unknown, although according to our results, it is possible that they could participate in the regulation of haematopoiesis.…”

Section: Discussionmentioning

confidence: 69%

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

et al. 2010

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Transient reactive oxygen species (ROS) production is currently proving to be an important mechanism in the regulation of intracellular signalling, but reports showing the involvement of ROS in important biological processes, such as cell differentiation, are scarce. In this study, we show for the first time that ROS production is required for megakaryocytic differentiation in K562 and HEL cell lines and also in human CD34 þ cells. ROS production is transiently activated during megakaryocytic differentiation, and such production is abolished by the addition of different antioxidants (such as N-acetyl cysteine, trolox, quercetin) or the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium. The inhibition of ROS formation hinders differentiation. RNA interference experiments have shown that a p22 phoxdependent NADPH oxidase activity is responsible for ROS production. In addition, the activation of ERK, AKT and JAK2 is required for differentiation, but the activation of phosphatidylinositol 3-kinase and c-Jun N-terminal kinase seems to be less important. When ROS production is prevented, the activation of these signalling pathways is partly inhibited. Taken together, these results show that NADPH oxidase ROS production is essential for complete activation of the main signalling pathways involved in megakaryocytopoiesis to occur. We suggest that this might also be important for in vivo megakaryocytopoiesis.

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Section: Discussionmentioning

confidence: 69%

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

et al. 2010

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“…In addition, increased production of ROS in HSCs from TSC1 -/ -mice has been attributed to the elevation of mitochondrial biogenesis and oxidative activities (23). However, compared to their progeny, HSCs are dormant and have fewer mitochondria (129,130). It has also been shown that HSCs primarily utilize glycolysis rather than mitochondrial oxidative phosphorylation for adenosine triphosphate production (5).…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

“…Five different NOXs are expressed in different tissues or cells with distinctive functions and mechanisms of regulation in a tissue-or cell-specific manner (16, 85). The expression of NOX1, 2, and 4 and various regulatory subunits of NOXs has been detected in human HSCs (129,130). It was estimated that NOX-mediated extramitochondrial oxygen consumption accounts for about half of the endogenous cell respiration in human HSCs (130).…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

Shao

Luo

Zhou

2014

Antioxidants & Redox Signaling

265

218

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Significance: Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Recent Advances: Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Critical Issues: Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. Future Directions: In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression.

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“…This idea is supported by the study of Spiegel et al [12] demonstrating the influence of adrenergic stimuli on HPC motility, proliferation, and repopulation. In addition, antioxidative treatment or inhibition of p38/mitogen-activated protein kinase (MAPK) signaling restored HPC growth in the presence of adrenergic stimuli [12,22]. Also, Liu et al [23] showed that the hypercatecholaminergic state that follows HS and resuscitation enhances neutrophil mobilization and that its effects can be blocked by prior treatment with propranolol.…”

Section: Elhassan Et Almentioning

confidence: 99%

Beta-Blockade Prevents Hematopoietic Progenitor Cell Suppression after Hemorrhagic Shock

Elhassan¹,

Hannoush²,

Sifri³

et al. 2011

Surgical Infections

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Background: Severe injury is accompanied by sympathetic stimulation that induces bone marrow (BM) dysfunction by both suppression of hematopoietic progenitor cell (HPC) growth and loss of cells via HPC mobilization to the peripheral circulation and sites of injury. Previous work demonstrated that beta-blockade (BB) given prior to tissue injury both reduces HPC mobilization and restores HPC colony growth within the BM. This study examined the effect and timing of BB on BM function in a hemorrhagic shock (HS) model. Methods: Male Sprague-Dawley rats underwent HS via blood withdrawal, maintaining the mean arterial blood pressure at 30-40 mm Hg for 45 min, after which the extracted blood was reinfused. Propranolol (10 mg/kg) was given either prior to or immediately after HS. Blood pressure, heart rate, BM cellularity, and death were recorded. Bone marrow HPC growth was assessed by counting colony-forming unit-granulocyte-, erythrocyte-, monocyte-, megakaryocyte (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming uniterythroid (CFU-E) cells. Results: Administration of BB prior to injury restored HPC growth to that of naïve animals (CFU-GEMM 59 ± 11 vs. 61 ± 4, BFU-E 68 ± 9 vs. 73 ± 3, and CFU-E 81 ± 35 vs. 78 ± 14 colonies/plate). Beta-blockade given after HS increased the growth of CFU-GEMM, BFU-E, and CFU-E significantly and improved BM cellularity compared with HS alone. The mortality rate was not increased in the groups receiving BB. Conclusion: Administration of propranolol either prior to injury or immediately after resuscitation significantly reduced post-shock BM suppression. After HS, BB may improve BM cellularity by decreasing HPC mobilization. Therefore, the early use of BB post-injury may play an important role in attenuating the BM dysfunction accompanying HS.

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Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and produce constitutively reactive oxygen species

Cited by 130 publications

References 33 publications

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

Beta-Blockade Prevents Hematopoietic Progenitor Cell Suppression after Hemorrhagic Shock

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