Effects of methoxylation of apocynin and analogs on the inhibition of reactive oxygen species production by stimulated human neutrophils

Worm, Edwin van den; Beukelman, C.J.; Berg, A. J. J. van den; Kroes, B. H.; Labadie, R. P.; Dijk, Hans van

doi:10.1016/s0014-2999(01)01516-3

Cited by 161 publications

(102 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…29 It does not, however, obstruct the phagocytic or other defense roles of granulocytes including intracellular killing, 26 and so may be widely used as an inhibitor of NOX. 30,31 Obviously, preclinical in-vivo studies are needed before the use of apocynin as an alternative to ADT for radiation sensitization in PC can be explored in clinical trails, but our findings establish a proofof-principle for this concept. P=0.001 Figure 5 The effect of apocynin on the in-vitro response of 22Rv1 cells to a single dose of 3 Gy radiation.…”

Section: Discussionmentioning

confidence: 76%

Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase

Monardo

Bryskin

et al. 2009

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Androgen deprivation therapy (ADT) facilitates the response of prostate cancer (PC) to radiation. Androgens have been shown to induce elevated basal levels of reactive oxygen species (ROS) in PC, leading to adaptation to radiation-induced cytotoxic oxidative stress. Here, we show that androgens increase the expression of p22 phox and gp91 phox subunits of NADPH oxidase (NOX) and ROS production by NOX2 and NOX4 in PC. Pre-radiation treatment of 22Rv1 human PC cells with NOX inhibitors sensitize the cells to radiation similarly to ADT, suggesting that their future usage may spare the need for adjuvant ADT in PC patients undergoing radiation.

show abstract

Section: Discussionmentioning

confidence: 76%

Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase

Monardo

Bryskin

et al. 2009

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

show abstract

“…This effect was not observed in vitro. Inhibition of the PMA-induced oxidation was observed with AEBSF (21) and apocynin (22), two other inhibitors of NADPH oxidase.…”

Section: Confirmation Of Redox Potential-preliminary Experimentsmentioning

confidence: 99%

Imaging Dynamic Redox Changes in Mammalian Cells with Green Fluorescent Protein Indicators

Dooley

Dore

Hanson

et al. 2004

Journal of Biological Chemistry

701

698

View full text Add to dashboard Cite

Changes in the redox equilibrium of cells influence a host of cell functions. Alterations in the redox equilibrium are precipitated by changing either the glutathione/glutathione-disulfide ratio (GSH/GSSG) and/or the reduced/oxidized thioredoxin ratio. Redox-sensitive green fluorescent proteins (GFP) allow real time visualization of the oxidation state of the indicator. Ratios of fluorescence from excitation at 400 and 490 nm indicate the extent of oxidation and thus the redox potential while canceling out the amount of indicator and the absolute optical sensitivity. Because the indicator is genetically encoded, it can be targeted to specific proteins or organelles of interest and expressed in a wide variety of cells and organisms. We evaluated roGFP1 (GFP with mutations C48S, S147C, and Q204C) and roGFP2 (the same plus S65T) with physiologically or toxicologically relevant oxidants both in vitro and in living mammalian cells. Furthermore, we investigated the response of the redox probes under physiological redox changes during superoxide bursts in macrophage cells, hyperoxic and hypoxic conditions, and in responses to H 2 O 2 -stimulating agents, e.g. epidermal growth factor and lysophosphatidic acid.Cells have elaborate homeostatic mechanisms to regulate the thiol-disulfide redox status of their internal compartments. Most thiol groups within the cytoplasm are normally reduced. Very few are present as disulfides. It has been speculated that the cytoplasm is reducing because many metabolic reactions evolved before oxygen became abundant in the atmosphere (1). Modest alterations in the thiol-disulfide equilibrium could have major consequences in the cell, including defective protein folding or enzyme activity (because many enzymes have a cysteine in their active site). When excess oxidation overwhelms the reductive capabilities of the cell, death results. Despite the dangers of excessive oxidation, cells sometimes use redox adjustments as signaling events, such as in the activation of transcription factors (NF-B and AP-1), caspases, protein tyrosine phosphatases, or GTPases (Ras). Thus, changes in the redox equilibrium influence a host of cell functions, including but not limited to growth, stress responses, differentiation, metabolism, cell cycle, communication, migration, gene transcription, ion channels, and immune responses (for reviews see Refs. 2-6). Alterations in the redox equilibrium are reflected in changes of the glutathione/glutathione-disulfide ratio (GSH/ GSSG) and the reduced/oxidized thioredoxin ratio. Glutathione is found in high concentrations in cells (5-10 mM) and is considered to be the major player in maintaining intracellular redox equilibrium. Ratios of GSH to GSSG are reported to range from 100 to 300:1 (7, 8), but these measurements have been problematic because they require destruction of the tissue, during which great care must be taken not to allow further oxidation. The major source of error is the determination of GSSG concentration, because this species is at low abundance yet is ...

show abstract

“…We cotreated IFN-␥-activated primary microglia with 10 g/ml myelin and apocynin, a specific inhibitor of the NADPH-oxidase complex ( Van der Worm et al, 2001), for 24 h. Apocynin treatment reversed the transcriptional downregulation of TNF-␣, iNOS, IL-1␤, MIP-1␣, and IP-10 by myelin phagocytosis (Fig. 7A) (supplemental Table 1, available at www.jneurosci.org as supplemental material).…”

Section: Inhibiting Assembly Of Nadph-oxidase Complex Reverses the Domentioning

confidence: 99%

Suppression of Microglial Inflammatory Activity by Myelin Phagocytosis: Role of p47-PHOX-Mediated Generation of Reactive Oxygen Species

Liu¹,

Hao²,

Letièmbre³

et al. 2006

J. Neurosci.

111

View full text Add to dashboard Cite

Multiple sclerosis (MS) is pathologically characterized by inflammatory demyelination and neuronal injury. Although phagocytosis of myelin debris by microglia and macrophages in acute MS lesions is well documented, its pathophysiological significance is unclear. Using real-time quantitative PCR, flow cytometry, ELISA, and reactive oxygen species (ROS) measurement assays, we demonstrated that phagocytosis of myelin modulates activation of microglial cells prestimulated by interferon-␥ (IFN-␥) or a combination of IFN-␥ and lipopolysaccharide with a biphasic temporal pattern, i.e., enhanced production of proinflammatory mediators during the first phase (Յ6 h), followed by suppression during the second (6 -24 h) phase. In this second phase, myelin phagocytosis leads to an enhanced release of prostaglandin E2 and ROS in microglia, whereas the production of anti-inflammatory cytokines (particularly interleukin-10) remains unchanged. Suppression of inflammatory microglial activation by myelin phagocytosis was reversed by treatment with superoxide dismutase and catalase, by inhibition of the NADPH-oxidase complex, or by specific knockdown of the NADPH-oxidase-required adaptor p47-phagocyte oxidase (PHOX). Furthermore, we observed that myelin phagocytosis destabilized tumor necrosis factor-␣ and interferon-induced protein-10 mRNA through an adenine-uridine-rich elements-involved mechanism, which was reversed by blocking the function of NADPH-oxidase complex. We conclude that phagocytosis of myelin suppresses microglial inflammatory activities via enhancement of p47-PHOX-mediated ROS generation. These results suggest that intervention in ROS generation could represent a novel therapeutic strategy to reduce neuroinflammation in MS.

show abstract

Effects of methoxylation of apocynin and analogs on the inhibition of reactive oxygen species production by stimulated human neutrophils

Cited by 161 publications

References 29 publications

Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase

Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase

Imaging Dynamic Redox Changes in Mammalian Cells with Green Fluorescent Protein Indicators

Suppression of Microglial Inflammatory Activity by Myelin Phagocytosis: Role of p47-PHOX-Mediated Generation of Reactive Oxygen Species

Contact Info

Product

Resources

About