Effects of menadione, a reactive oxygen generator, on leukotriene secretion from RBL-2H3 cells.
Reactive oxygen species (ROS) are produced in various cells and affect many biological processes. We previously reported that 2-methyl-1,4-naphtoquinone (menadione) inhibited Ca(2+) influx from the extracellular medium and exocytosis evoked by antigen stimulation in the mast cell line, RBL-2H3. Mast cells release various inflammatory mediators such as leukotrienes (LTs) and cytokines in addition to the exocytotic secretion of histamine. In this study, we investigated the effects of menadione on LT release in RBL-2H3. Treatment of RBL cells with menadione inhibited LTC(4) secretion induced by antigen stimulation. To elucidate the mechanism of this inhibition, we examined the effects of menadione on the activation process of 5-lipoxygenase that is responsible for the synthesis of LTs from arachidonic acid. Menadione did not affect the phosophorylation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, which regulates phosphorylation of 5-lipoxygenase. However, menadione inhibited the translocation of 5-lipoxygenase from the cytoplasm to the nuclear membrane. Together with the result that LT secretion was severely impaired in the absence of extracellular Ca2(2+), it is suggested that ROS produced by menadione inhibited LT secretion through impaired Ca2(2+) influx and 5-lipoxygenase translocation to the nuclear membrane.
Kawamura
Fumio
F
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Nakanishi
Mamoru
M
Hirashima
Naohide
N
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000941:Antigens; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000941:Antigens; D017382:Reactive Oxygen Species; D017997:Leukotriene C4; D024483:Vitamin K 3; D001094:Arachidonate 5-Lipoxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium