Effects of 2-Methyl-1,4-naphtoquinone (Menadione) on Cellular Signaling in RBL-2H3 Cells

Kawamura, Fumio; Hirashima, Naohide; Furuno, Tadahide; Nakanishi, Mamoru

doi:10.1248/bpb.29.605

Cited by 19 publications

(15 citation statements)

References 24 publications

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“…In the absence of extracellular Ca 2ϩ , LTC 4 secretion was reduced to about 10% of control. As reported in our previous paper, 16) menadione inhibits Ca 2ϩ influx from the extracellular medium, therefore, one of the major reasons for inhibition is thought to be a reduction in the concentration of intracellular Ca 2ϩ .…”

Section: Inhibition Of Lc 4 Secretionsupporting

confidence: 52%

“…As we reported previously, we investigated the effects of ROS that is produced within cells on mast cell signaling. 16) In mast cells, antigen stimulation causes the elevation of intracellular Ca 2ϩ concentration, and menadione dose dependently inhibits Ca 2ϩ increase and exocytotic release of histamine (degranulation) dose-dependently. LTs are synthesized after cell activation and secreted from mast cells to cause inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…We reported that menadione inhibits Ca 2ϩ influx. 16) Furthermore, H 2 O 2 impairs the elevation of the intracellular Ca 2ϩ concentration evoked by antigen stimulation in mast cells. 29) N-terminal b-sandwich domain of 5-lipoxygenase functions as a C2 domain and the enzyme activity is regulated by Ca 2ϩ .…”

Section: Discussionmentioning

confidence: 99%

“…We reported that intracellular ROS produced by menadione, 2-methyl-1,4-naphtoquinone, together with reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) and quinone oxidoreductase inhibited antigen-induced degranulation caused by impaired Ca 2ϩ influx from the extracellular medium, without affecting Ca 2ϩ release from the intracellular Ca 2ϩ stores. 16) In the present study, we investigated the effects of menadione on the secretion of another inflammatory mediator, leukotriene C 4 (LTC 4 ). We found that ROS produced by menadione inhibits LTC 4 secretion.…”

mentioning

confidence: 99%

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Effects of Menadione, a Reactive Oxygen Generator, on Leukotriene Secretion from RBL-2H3 Cells

Kawamura

Nakanishi

Hirashima

2010

Biological & Pharmaceutical Bulletin

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Section: Inhibition Of Lc 4 Secretionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Menadione, a Reactive Oxygen Generator, on Leukotriene Secretion from RBL-2H3 Cells

Kawamura

Nakanishi

Hirashima

2010

Biological & Pharmaceutical Bulletin

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“…Because menadione is a naphthoquinone that leads to the production of reactive oxygen species inside the cells and causes dramatic changes in mitochondrial metabolism (Gerasimenko et al, 2002;Criddle et al, 2006;Kawamura et al, 2006), we examined whether the selective inhibitors of QR2 were able to protect against menadione-induced apoptosis. The number of menadione-treated cells stained with either SYTO 16 or ethidium bromide increased by 68 and 77%, indicating that menadione exerts an apoptotic effect on hippocampal neuronal cells (Fig.…”

Section: Qr2 Inhibitors Protect Hippocampal Cells Against Menadione-imentioning

confidence: 99%

Loss of Quinone Reductase 2 Function Selectively Facilitates Learning Behaviors

Benoit¹,

Bastianetto²,

Brouillette³

et al. 2010

J. Neurosci.

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High levels of reactive oxygen species (ROS) are associated with deficits in learning and memory with age as well as in Alzheimer's disease. Using DNA microarray, we demonstrated the overexpression of quinone reductase 2 (QR2) in the hippocampus in two models of learning deficits, namely the aged memory impaired rats and the scopolamine-induced amnesia model. QR2 is a cytosolic flavoprotein that catalyzes the reduction of its substrate and enhances the production of damaging activated quinone and ROS. QR2-like immunostaining is enriched in cerebral structures associated with learning behaviors, such as the hippocampal formation and the temporofrontal cortex of rat, mouse, and human brains. In cultured rat embryonic hippocampal neurons, selective inhibitors of QR2, namely S26695 and S29434, protected against menadione-induced cell death by reversing its proapoptotic action. S26695 (8 mg/kg) also significantly inhibited scopolamine-induced amnesia. Interestingly, adult QR2 knock-out mice demonstrated enhanced learning abilities in various tasks, including Morris water maze, object recognition, and rotarod performance test. Other behaviors related to anxiety (elevated plus maze), depression (forced swim), and schizophrenia (prepulse inhibition) were not affected in QR2-deficient mice. Together, these data suggest a role for QR2 in cognitive behaviors with QR2 inhibitors possibly representing a novel therapeutic strategy toward the treatment of learning deficits especially observed in the aged brain.

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Umbilical Cord Derived Mast Cells as Models for the Study of Inflammatory Diseases

Kourelis¹,

Kempuraj²,

Manola³

et al. 2009

Perinatal Stem Cells

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Effects of 2-Methyl-1,4-naphtoquinone (Menadione) on Cellular Signaling in RBL-2H3 Cells

Cited by 19 publications

References 24 publications

Effects of Menadione, a Reactive Oxygen Generator, on Leukotriene Secretion from RBL-2H3 Cells

Effects of Menadione, a Reactive Oxygen Generator, on Leukotriene Secretion from RBL-2H3 Cells

Loss of Quinone Reductase 2 Function Selectively Facilitates Learning Behaviors

Umbilical Cord Derived Mast Cells as Models for the Study of Inflammatory Diseases

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