Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst

Chatterjee, Mainak; Saluja, Rohit; Kumar, Vipul; Jyoti, Anupam; Jain, Girish Kumar; Barthwal, Manoj Kumar; Dikshit, Madhu

doi:10.1016/j.freeradbiomed.2008.06.028

Cited by 30 publications

(26 citation statements)

References 53 publications

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“…nNOS is well-documented NOS isoform in neutrophils (27,29,30,47); we found similar level of expression during neutrophils maturation, suggesting continued and constitutive presence of nNOS during neutrophil maturation (Fig. 3).…”

Section: Discussionsupporting

confidence: 72%

“…Specifically, rat neutrophils constitutively express nNOS and generate higher levels of NO; whereas human neutrophils express low level of enzyme at mRNA and protein level. The previous reports from this laboratory have shown the presence of nNOS and iNOS and their subcellular localization but failed to detect eNOS in peripheral rat PMNs (29,30).…”

mentioning

confidence: 73%

“…The presence of nNOS and iNOS in rat peripheral PMNs has been well documented (15,27,29,30,42,43). As neutrophils precursors constitute the major fraction of bone marrow niche, NO produced from these cells might act as a paracrine effector to regulate hematopoiesis in the bone marrow.…”

Section: Discussionmentioning

confidence: 98%

“…nNOS expression was stable during maturation, iNOS consistently increased with maturation (Figs. 3A and 3B), whereas eNOS was down regulated that could be the reason that most of the researchers failed to find eNOS in neutrophils (14,15,27,29,30,42). Amin et al (28) reported that iNOS was below the detectable level in neutrophils by Western blotting analysis.…”

Section: Discussionmentioning

confidence: 99%

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Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

et al. 2010

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Previous studies from this laboratory have demonstrated importance of neutrophilderived nitric oxide (NO) in free radical generation, characterized nitric oxide synthase (NOS) isoforms, and have reported subcellular distribution of NOS in rat peripheral neutrophils. Maximum number of neutrophils are added per day to the circulation from bone marrow, thus neutrophils might add substantial amount of NO in the bone marrow. NO generating ability and NOS isoforms characteristics in bone marrow neutrophil precursor cells is, however, still unexplored. This study was, therefore, undertaken to investigate NO generation ability and the molecular/biochemical characteristics of NOS isoforms in neutrophil precursor cells. The neutrophil precursors were separated on Percoll density gradient and characterized by Giemsa staining, CD markers, and by their size and granularity at various stages of maturation as Bands 1, 2, and 3. Mature neutrophils were efficient in free radical generation and phagocytosis, whereas immature cells had more mitochondria and myeloperoxidase. Amount of NO augmented from immature to mature neutrophils as assessed by fluorescent probe DAF-2DA and Griess reagent. Measurement of NOS enzyme activity further confirmed the functional status of NOS in these cells. NOS isoforms were differentially expressed during neutrophil maturation as confirmed by enzyme activity, Western blotting, flowcytometry, and RT-PCR. Expression of nNOS was predominantly stable in all the stages of neutrophil maturation. iNOS expression was, however, consistently augmented during maturation, whereas eNOS expression was downregulated with neutrophil maturation. Furthermore, all NOS isoforms proteins were distributed in cytosol as well as nucleus as assessed by confocal microscopy. This study for the first time report biochemical and molecular characteristics of NOS isoforms in rat neutrophil precursor cells. ' 2010 International Society for Advancement of Cytometry Key terms nitric oxide; NOS; neutrophils; neutrophil precursor cells; maturation NEUTROPHILS (PMNs) are orchestrating cells of the innate immune system (1,2), circulating through the body and extravasating to the sites of infection and injury, to perform important roles in the host defense. This process involves recruitment of lysosomes and various types of granules to release proteolytic enzymes, antimicrobial peptides, and free radical formation (1,2). PMN development in the bone marrow has classically been divided into six stages myeloblasts (MBs), promyelocytes (PMs), myelocytes (MCs), metamyelocytes (MMs), band cells (BCs), and segmented neutrophil on the basis of cell size, nuclear morphology, and granule content (3,4). Production of these cells is continuous to provide the continual demand for the tissues and mostly to maintain the circulating pool in the blood.Nitric oxide (NO), a versatile signaling molecule, mediates immune response, vasodilation, neurotransmission, proliferation, and apoptosis (5-8). NO is synthesized by a class of NADPH-dependent N...

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Section: Discussionsupporting

confidence: 72%

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confidence: 73%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

et al. 2010

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“…In this way, erythrocytes are more important because they have the particularity to be the first line of antioxidant defenses and are exposed to decreases of their antioxidant capacity (Chatterjee et al, 2008). Considering these points together, we have conducted an in vitro study to show the impact of the high doses of AA on human cells exempted from plasma milieu and to try to shed light onto the mechanistic sides.…”

Section: Introductionmentioning

confidence: 99%

Proposed Insights in the Pharmaco-Dynamic Theory of Ascorbate Pro-Oxidant Activity

Kerboua¹,

Haiba²,

Bendjemia³

et al. 2016

OnLine Journal of Biological Sciences

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Ascorbate pro-drug theory promising possible effective and nontoxic treatment is intensively examined and centered on the importance of both extracellular and intra-cellular effects of ascorbate. In this study, we sought to determine the in vitro cell responsiveness in a plasma free milieu with or without an extracellular catalyst and/or hydrogen peroxide. This project brought to light how ascorbic acid would react to in a Red Blood Cell (RBC) suspension by using the two anti-oxidant pathways. We demonstrated that while ascorbate doesn't require an extracellular metal catalyst to induce cell damage via the lipid peroxidation pathway, the protein-centered metal pathway could be enhanced by a divalent cation, hydrogen peroxide or both. The current lack of understanding of ascorbate potential mechanism excites us to propose some insights for the vitamine C pharmacologic dose pro-oxidant activity.

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Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endothelium

2009

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Circulating levels of vitamin C (ascorbate) are low in patients with sepsis. Parenteral administration of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of sepsis, intravenous ascorbate injection increases survival and protects several microvascular functions, namely, capillary blood flow, microvascular permeability barrier, and arteriolar responsiveness to vasoconstrictors and vasodilators. The effects of parenteral ascorbate on microvascular function are both rapid and persistent. Ascorbate quickly accumulates in microvascular endothelial cells, scavenges reactive oxygen species, and acts through tetrahydrobiopterin to stimulate nitric oxide production by endothelial nitric oxide synthase. A major reason for the long duration of the improvement in microvascular function is that cells retain high levels of ascorbate, which alter redox-sensitive signaling pathways to diminish septic induction of NADPH oxidase and inducible nitric oxide synthase. These observations are consistent with the hypothesis that microvascular function in sepsis may be improved by parenteral administration of ascorbate as an adjuvant therapy.

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Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst

Cited by 30 publications

References 53 publications

Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

Proposed Insights in the Pharmaco-Dynamic Theory of Ascorbate Pro-Oxidant Activity

Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endothelium

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