High oxidative stress adversely affects NFκB mediated induction of inducible nitric oxide synthase in human neutrophils: Implications in chronic myeloid leukemia

Singh, Abhishek Kumar; Awasthi, Deepika; Dubey, Megha; Nagarkoti, Sheela; Kumar, Ashutosh; Chandra, Tulika; Barthwal, Manoj Kumar; Tripathi, Anil Kumar; Dikshit, Madhu

doi:10.1016/j.niox.2016.06.002

Cited by 29 publications

(48 citation statements)

References 87 publications

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“…Generation of RNS is TLR-dependent metabolic process and is associated with NFκB activation (Parker et al 2005 ; McCoy and O’Neill 2008 ). In addition, RNS synthesis is adversely regulated by oxidative stress (Singh et al 2016 ) and therefore is related to CYP activation. We characterized the RNS generation by the level of nitrites (Griess reaction) in culture medium of cells treated with C 60 fullerenes and their nanocomplexes with Cis and Dox.…”

Section: Resultsmentioning

confidence: 99%

C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes

et al. 2018

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BackgroundC60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C60 fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. The main aim of this study was to investigate the effect of C60 fullerene and its nanocomplexes with anticancer drugs on human phagocyte metabolic profile in vitro.MethodsAnalysis of the metabolic profile of phagocytes exposed to C60 fullerene in vitro revealed augmented phagocytic activity and down-regulated reactive nitrogen species generation in these cells. Additionally, cytofluorimetric analysis showed that C60 fullerene can exert direct cytotoxic effect on normal and transformed phagocytes through the vigorous induction of intracellular reactive oxygen species generation.ResultsCytotoxic action as well as the pro-oxidant effect of C60 fullerene was more pronounced toward malignant phagocytes. At the same time, C60 fullerenes have the ability to down-regulate the pro-oxidant effect of cisplatin on normal cells. These results indicate that C60 fullerenes may influence phagocyte metabolism and have both pro-oxidant and antioxidant properties.ConclusionsThe antineoplastic effect of C60 fullerene has been observed by direct toxic effect on tumor cells, as well as through the modulation of the functions of effector cells of antitumor immunity.

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Section: Resultsmentioning

confidence: 99%

C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes

et al. 2018

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“…NO-mediated production of ROS in PMNs has been reported; however, the role of NO is biphasic on the production of ROS in PMNs after treatment with ascorbate, arachidonic acid, and fMLP. The production of ROS was increased in lower NO concentrations, whereas higher NO concentrations inhibited ROS production through the inhibition of NADPH oxidase or ROS clearaway [ 28 ]. So, we presumed that ROS production induced by CaSR seemed to be more closely related to NO.…”

Section: Discussionmentioning

confidence: 99%

Expression and Role of the Calcium‐Sensing Receptor in Rat Peripheral Blood Polymorphonuclear Neutrophils

Zhai

Cui

Zou

et al. 2017

Oxidative Medicine and Cellular Longevity

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The calcium-sensing receptors (CaSRs) play an important role in many tissues and organs that are involved in inflammatory reactions. Peripheral blood polymorphonuclear neutrophils (PMNs) are important inflammatory cells. However, the expression and functions of CaSR in peripheral blood PMNs are still not reported. In this study, we collected rat peripheral blood PMNs to observe the relationship between CaSR and PMNs. From the results, we found first that the CaSR protein was expressed in PMNs, and it increased after PMNs were activated with fMLP. In addition, CaSR activator cincalcet promoted the expression of CaSR and P-p65 (NF-κB signaling pathway protein) and Bcl-xl (antiapoptosis protein), and it increased the secretion of interleukin-6 (IL-6) and myeloperoxidase (MPO); meanwhile, it decreased proapoptosis protein Bax expression and the production of IL-10 and reactive oxygen species (ROS). At the same time, cincalcet also decreased the PMN apoptosis rate analyzed by flow cytometry. However, CaSR inhibitor NPS-2143 and NF-κB signaling pathway inhibitor PDTC reverse the results cited earlier. All of these results indicated that CaSR can regulate PMN functions and status to play a role in inflammation, which is probably through the NF-κB signaling pathway.

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“…Extracellular NO release was quantitated using DAF‐2 (10 µM) that directly binds with NO in extracellular medium and gives a fluorescence product, which was detected using a fluorimeter. Intracellular superoxide radicals’ generation was analyzed by using redox‐sensitive dihydroethidium (DHE) probe . Briefly, cells (1 × 10 5 ) were loaded with DAF‐2DA (10 µM) or DHE (10µM) for 15 min at 37°C and the fluorescence of 10,000 cells was acquired on FACS Calibur and subsequently analyzed using Cell Quest programme (Becton Dickinson) .…”

Section: Methodsmentioning

confidence: 99%

“…Intracellular superoxide radicals’ generation was analyzed by using redox‐sensitive dihydroethidium (DHE) probe . Briefly, cells (1 × 10 5 ) were loaded with DAF‐2DA (10 µM) or DHE (10µM) for 15 min at 37°C and the fluorescence of 10,000 cells was acquired on FACS Calibur and subsequently analyzed using Cell Quest programme (Becton Dickinson) . PMA (30 nM, for 30 min) was used to induce generation of superoxide and other ROS …”

Section: Methodsmentioning

confidence: 99%

“…33 Briefly, cells (1 × 10 5 ) were loaded with DAF-2DA (10 µM) or DHE (10µM) for 15 min at 37 • C and the fluorescence of 10,000 cells was acquired on FACS Calibur and subsequently analyzed using Cell Quest programme (Becton Dickinson). 33 PMA (30 nM, for 30 min) was used to induce generation of superoxide and other ROS. 34 NO production in K562 and K562 iNOS cells was also determined by measuring nitrite content, the metabolic end product of NO formation using modified Griess reagent (0.1% aqueous N-(l-naphthyl)ethylenediamine dihydrochloride, 1% sulphanilamide and 2.5% phosphoric acid) as described earlier.…”

Section: Assessment Of No and Reactive Oxygen Species (Ros) Generationmentioning

confidence: 99%

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Augmentation of iNOS expression in myeloid progenitor cells expedites neutrophil differentiation

Sadaf

Singh

Awasthi

et al. 2019

Journal of Leukocyte Biology

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Neutrophils play important role in immunity and inflammation through diverse mechanisms. Reports from this lab and others have demonstrated involvement of NO in neutrophil adhesion, chemotaxis, bacterial killing, reactive oxygen species generation, neutrophil extracellular traps’ formation, and apoptosis. Constitutive expression of iNOS in human neutrophils has also been documented. The role of NO‐iNOS in neutrophil differentiation however remains ill‐defined. The present study was undertaken to understand the role of NO generated from iNOS in the neutrophil differentiation by using iNOS‐overexpressing K562 cells (K562iNOS) and iNOS‐deficient murine progenitor cells (lineage negative cells; lin‐ve). We observed that iNOS overexpression led to increased neutrophilic differentiation in K562 cells; more specifically an early and accelerated neutrophilic differentiation was spotted in K562iNOS. These observations were further validated using iNOS knockout lin‐ve cells or hematopoietic progenitor cells that exhibited delayed neutrophil differentiation in comparison to its wild‐type counterpart. In addition, a significant increase in the gene expression of iNOS during neutrophilic differentiation of CD34+ hematopoietic stem and progenitor cells derived from human bone marrow further substantiates importance of iNOS in neutrophil differentiation. Moreover, a significant increase in NO generation during neutrophil differentiation was observed and enhanced neutrophil differentiation with NO donor was also observed, implying the importance of NO in neutrophil differentiation. Collectively, using alternative approaches, we demonstrated that neutrophil differentiation is significantly influenced by iNOS or NO, suggesting the possibility of exploiting this novel link for therapeutic aspects of NO generated from iNOS and neutrophil differentiation in hematopoiesis‐related disorders.

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High oxidative stress adversely affects NFκB mediated induction of inducible nitric oxide synthase in human neutrophils: Implications in chronic myeloid leukemia

Cited by 29 publications

References 87 publications

C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes

C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes

Expression and Role of the Calcium‐Sensing Receptor in Rat Peripheral Blood Polymorphonuclear Neutrophils

Augmentation of iNOS expression in myeloid progenitor cells expedites neutrophil differentiation

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